Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Novel Adiponectin Receptor Agonist Inhibits Cholangiocarcinoma via Adenosine Monophosphate-activated Protein Kinase

Author(s): Khac Cuong Bui, Thi Mai Ly Nguyen, Samarpita Barat, Tim Scholta, Jun Xing, Vikas Bhuria, Bence Sipos, Ludwig Wilkens, Linh Toan Nguyen, Huu Song Le, Thirumalaisamy P. Velavan, Przemyslaw Bozko* and Ruben R. Plentz*

Volume 31, Issue 28, 2024

Published on: 23 January, 2024

Page: [4534 - 4548] Pages: 15

DOI: 10.2174/0109298673254969231122114107

Price: $65

Abstract

Background: Cholangiocarcinoma (CCA) has a poor prognosis and only limited palliative treatment options. The deficiency of adiponectin and adenosine monophosphate-activated protein kinase (AMPK) signaling was reported in several malignancies, but the alteration of these proteins in CCA is still unclear.

Objectives:: This study aimed to assess the role of adiponectin and AMPK signaling in CCA. Furthermore, AdipoRon, a novel adiponectin receptor (AdipoR) agonist, was evaluated in vitro and in vivo as a new anti-tumor therapy for CCA.

Methods: The expression of AdipoR1 and p-AMPKα in human tissue microarrays (TMAs) was evaluated by immunohistochemistry staining (IHC). The effect of 2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide (AdipoRon) was investigated in vitro with proliferation, crystal violet, migration, invasion, colony formation, senescence, cell cycle and apoptosis assays and in vivo using a CCA engineered mouse model (AlbCre/LSL-KRASG12D/p53L/L). RT-qPCR and western blot methods were applied to study molecular alterations in murine tissues.

Results: AdipoR1 and p-AMPKα were impaired in human CCA tissues, compared to adjacent non-tumor tissue. There was a positive correlation between the AdipoR1 and p-AMPKα levels in CCA tissues. Treatment with AdipoRon inhibited proliferation, migration, invasion and colony formation and induced apoptosis in a time- and dose-dependent manner in vitro (p<0.05). In addition, AdipoRon reduced the number of CCA and tumor volume, prolonged survival, and decreased metastasis and ascites in the treated group compared to the control group (p<0.05).

Conclusions: AdipoR1 and p-AMPKα are impaired in CCA tissues, and AdipoRon effectively inhibits CCA in vitro and in vivo. Thus, AdipoRon may be considered as a potential anti-tumor therapy in CCA.

« Previous Next »
[1]
Rizvi, S.; Gores, G.J. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology, 2013, 145(6), 1215-1229.
[http://dx.doi.org/10.1053/j.gastro.2013.10.013] [PMID: 24140396]
[2]
Zhou, S.; Zhao, Y.; Lu, Y.; Liang, W.; Ruan, J.; Lin, L.; Lin, H.; Huang, K. Cancer-specific survival in patients with cholangiocarcinoma after radical surgery: A Novel, dynamic nomogram based on clinicopathological features and serum markers. BMC Cancer, 2023, 23(1), 533.
[http://dx.doi.org/10.1186/s12885-023-11040-9] [PMID: 37308861]
[3]
Laurenzi, A.; Brandi, G.; Greco, F.; Prosperi, E.; Palloni, A.; Serenari, M.; Frega, G.; Ravaioli, M.; Rizzo, A.; Cescon, M. Can repeated surgical resection offer a chance of cure for recurrent cholangiocarcinoma? Langenbecks Arch. Surg., 2023, 408(1), 102.
[http://dx.doi.org/10.1007/s00423-023-02839-y] [PMID: 36826620]
[4]
Munugala, N.; Maithel, S.K.; Shroff, R.T. Novel biomarkers and the future of targeted therapies in cholangiocarcinoma: a narrative review. Hepatobiliary Surg. Nutr., 2022, 11(2), 253-266.
[http://dx.doi.org/10.21037/hbsn-20-475] [PMID: 35464290]
[5]
Sato, K.; Glaser, S.; Alvaro, D.; Meng, F.; Francis, H.; Alpini, G. Cholangiocarcinoma: Novel therapeutic targets. Expert Opin. Ther. Targets, 2020, 24(4), 345-357.
[http://dx.doi.org/10.1080/14728222.2020.1733528] [PMID: 32077341]
[6]
Cidon, E.U. Resectable cholangiocarcinoma: Reviewing the role of adjuvant strategies. Clin. Med. Insights Oncol., 2016, 10, CMO.S32821.
[http://dx.doi.org/10.4137/CMO.S32821] [PMID: 27199577]
[7]
Nguyen, M.L.T.; Toan, N.L.; Bozko, M.; Bui, K.C.; Bozko, P. Cholangiocarcinoma therapeutics: An update. Curr. Cancer Drug Targets, 2021, 21(6), 457-475.
[http://dx.doi.org/10.2174/1568009621666210204152028] [PMID: 33563168]
[8]
Shaib, Y.; El-Serag, H. The epidemiology of cholangiocarcinoma. Semin. Liver Dis., 2004, 24(2), 115-125.
[http://dx.doi.org/10.1055/s-2004-828889] [PMID: 15192785]
[9]
Bridgewater, J.; Galle, P.R.; Khan, S.A.; Llovet, J.M.; Park, J.W.; Patel, T.; Pawlik, T.M.; Gores, G.J. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J. Hepatol., 2014, 60(6), 1268-1289.
[http://dx.doi.org/10.1016/j.jhep.2014.01.021] [PMID: 24681130]
[10]
Razumilava, N.; Gores, G.J. Cholangiocarcinoma. Lancet, 2014, 383(9935), 2168-2179.
[http://dx.doi.org/10.1016/S0140-6736(13)61903-0] [PMID: 24581682]
[11]
Valle, J.; Wasan, H.; Palmer, D.H.; Cunningham, D.; Anthoney, A.; Maraveyas, A.; Madhusudan, S.; Iveson, T.; Hughes, S.; Pereira, S.P.; Roughton, M.; Bridgewater, J. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N. Engl. J. Med., 2010, 362(14), 1273-1281.
[http://dx.doi.org/10.1056/NEJMoa0908721] [PMID: 20375404]
[12]
Valle, J.W.; Borbath, I.; Khan, S.A.; Huguet, F.; Gruenberger, T.; Arnold, D. Biliary cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol., 2016, 27(Suppl. 5), v28-v37.
[http://dx.doi.org/10.1093/annonc/mdw324] [PMID: 27664259]
[13]
Pajvani, U.B.; Du, X.; Combs, T.P.; Berg, A.H.; Rajala, M.W.; Schulthess, T.; Engel, J.; Brownlee, M.; Scherer, P.E. Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity. J. Biol. Chem., 2003, 278(11), 9073-9085.
[http://dx.doi.org/10.1074/jbc.M207198200] [PMID: 12496257]
[14]
Natarajan, R.; Salloum, F.N.; Fisher, B.J.; Kukreja, R.C.; Fowler, A.A., III Hypoxia inducible factor-1 upregulates adiponectin in diabetic mouse hearts and attenuates post-ischemic injury. J. Cardiovasc. Pharmacol., 2008, 51(2), 178-187.
[http://dx.doi.org/10.1097/FJC.0b013e31815f248d] [PMID: 18287886]
[15]
Chen, J.; Tan, B.; Karteris, E.; Zervou, S.; Digby, J.; Hillhouse, E.W.; Vatish, M.; Randeva, H.S. Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines. Diabetologia, 2006, 49(6), 1292-1302.
[http://dx.doi.org/10.1007/s00125-006-0194-7] [PMID: 16570162]
[16]
Achari, A.; Jain, S. Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. Int. J. Mol. Sci., 2017, 18(6), 1321.
[http://dx.doi.org/10.3390/ijms18061321] [PMID: 28635626]
[17]
Yamauchi, T.; Kamon, J.; Ito, Y.; Tsuchida, A.; Yokomizo, T.; Kita, S.; Sugiyama, T.; Miyagishi, M.; Hara, K.; Tsunoda, M.; Murakami, K.; Ohteki, T.; Uchida, S.; Takekawa, S.; Waki, H.; Tsuno, N.H.; Shibata, Y.; Terauchi, Y.; Froguel, P.; Tobe, K.; Koyasu, S.; Taira, K.; Kitamura, T.; Shimizu, T.; Nagai, R.; Kadowaki, T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature, 2003, 423(6941), 762-769.
[http://dx.doi.org/10.1038/nature01705] [PMID: 12802337]
[18]
Yamauchi, T.; Nio, Y.; Maki, T.; Kobayashi, M.; Takazawa, T.; Iwabu, M.; Okada-Iwabu, M.; Kawamoto, S.; Kubota, N.; Kubota, T.; Ito, Y.; Kamon, J.; Tsuchida, A.; Kumagai, K.; Kozono, H.; Hada, Y.; Ogata, H.; Tokuyama, K.; Tsunoda, M.; Ide, T.; Murakami, K.; Awazawa, M.; Takamoto, I.; Froguel, P.; Hara, K.; Tobe, K.; Nagai, R.; Ueki, K.; Kadowaki, T. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat. Med., 2007, 13(3), 332-339.
[http://dx.doi.org/10.1038/nm1557] [PMID: 17268472]
[19]
Fantuzzi, G. Adiponectin in inflammatory and immune-mediated diseases. Cytokine, 2013, 64(1), 1-10.
[http://dx.doi.org/10.1016/j.cyto.2013.06.317] [PMID: 23850004]
[20]
Robinson, K.; Prins, J.; Venkatesh, B. Clinical review: Adiponectin biology and its role in inflammation and critical illness. Crit. Care, 2011, 15(2), 221.
[http://dx.doi.org/10.1186/cc10021] [PMID: 21586104]
[21]
Takeuchi, T.; Adachi, Y.; Ohtsuki, Y.; Furihata, M. Adiponectin receptors, with special focus on the role of the third receptor, T-cadherin, in vascular disease. Med. Mol. Morphol., 2007, 40(3), 115-120.
[http://dx.doi.org/10.1007/s00795-007-0364-9] [PMID: 17874043]
[22]
An, W.; Bai, Y.; Deng, S.X.; Gao, J.; Ben, Q.W.; Cai, Q.C.; Zhang, H.G.; Li, Z.S. Adiponectin levels in patients with colorectal cancer and adenoma. Eur. J. Cancer Prev., 2012, 21(2), 126-133.
[http://dx.doi.org/10.1097/CEJ.0b013e32834c9b55] [PMID: 21960184]
[23]
Xu, X.T.; Xu, Q.; Tong, J.L.; Zhu, M.M.; Huang, M.L.; Ran, Z.H.; Xiao, S.D. Meta-analysis: Circulating adiponectin levels and risk of colorectal cancer and adenoma. J. Dig. Dis., 2011, 12(4), 234-244.
[http://dx.doi.org/10.1111/j.1751-2980.2011.00504.x] [PMID: 21791018]
[24]
Ishikawa, M.; Kitayama, J.; Kazama, S.; Hiramatsu, T.; Hatano, K.; Nagawa, H. Plasma adiponectin and gastric cancer. Clin. Cancer Res., 2005, 11(2), 466-472.
[http://dx.doi.org/10.1158/1078-0432.466.11.2] [PMID: 15701829]
[25]
Nakajima, T.E.; Yamada, Y.; Hamano, T.; Furuta, K.; Gotoda, T.; Katai, H.; Kato, K.; Hamaguchi, T.; Shimada, Y. Adipocytokine levels in gastric cancer patients: Resistin and visfatin as biomarkers of gastric cancer. J. Gastroenterol., 2009, 44(7), 685-690.
[http://dx.doi.org/10.1007/s00535-009-0063-5] [PMID: 19430715]
[26]
Goktas, S.; Yilmaz, M.I.; Caglar, K.; Sonmez, A.; Kilic, S.; Bedir, S. Prostate cancer and adiponectin. Urology, 2005, 65(6), 1168-1172.
[http://dx.doi.org/10.1016/j.urology.2004.12.053] [PMID: 15922427]
[27]
Michalakis, K.; Williams, C.J.; Mitsiades, N.; Blakeman, J.; Balafouta-Tselenis, S.; Giannopoulos, A.; Mantzoros, C.S. Serum adiponectin concentrations and tissue expression of adiponectin receptors are reduced in patients with prostate cancer: A case control study. Cancer Epidemiol. Biomarkers Prev., 2007, 16(2), 308-313.
[http://dx.doi.org/10.1158/1055-9965.EPI-06-0621] [PMID: 17301264]
[28]
Arisan, E.D.; Arisan, S.; Atis, G.; Palavan-Unsal, N.; Ergenekon, E. Serum adipocytokine levels in prostate cancer patients. Urol. Int., 2009, 82(2), 203-208.
[http://dx.doi.org/10.1159/000200801] [PMID: 19322011]
[29]
Mantzoros, C.; Petridou, E.; Dessypris, N.; Chavelas, C.; Dalamaga, M.; Alexe, D.M.; Papadiamantis, Y.; Markopoulos, C.; Spanos, E.; Chrousos, G.; Trichopoulos, D. Adiponectin and breast cancer risk. J. Clin. Endocrinol. Metab., 2004, 89(3), 1102-1107.
[http://dx.doi.org/10.1210/jc.2003-031804] [PMID: 15001594]
[30]
Chen, D.C.; Chung, Y.F.; Yeh, Y.T.; Chaung, H.C.; Kuo, F.C.; Fu, O.Y.; Chen, H.Y.; Hou, M.F.; Yuan, S.S.F. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett., 2006, 237(1), 109-114.
[http://dx.doi.org/10.1016/j.canlet.2005.05.047] [PMID: 16019138]
[31]
Dalamaga, M.; Diakopoulos, K.N.; Mantzoros, C.S. The role of adiponectin in cancer: A review of current evidence. Endocr. Rev., 2012, 33(4), 547-594.
[http://dx.doi.org/10.1210/er.2011-1015] [PMID: 22547160]
[32]
Kelesidis, I.; Kelesidis, T.; Mantzoros, C.S. Adiponectin and cancer: A systematic review. Br. J. Cancer, 2006, 94(9), 1221-1225.
[http://dx.doi.org/10.1038/sj.bjc.6603051] [PMID: 16570048]
[33]
Kamada, Y.; Matsumoto, H.; Tamura, S.; Fukushima, J.; Kiso, S.; Fukui, K.; Igura, T.; Maeda, N.; Kihara, S.; Funahashi, T.; Matsuzawa, Y.; Shimomura, I.; Hayashi, N. Hypoadiponectinemia accelerates hepatic tumor formation in a nonalcoholic steatohepatitis mouse model. J. Hepatol., 2007, 47(4), 556-564.
[http://dx.doi.org/10.1016/j.jhep.2007.03.020] [PMID: 17459514]
[34]
Yokota, T.; Oritani, K.; Takahashi, I.; Ishikawa, J.; Matsuyama, A.; Ouchi, N.; Kihara, S.; Funahashi, T.; Tenner, A.J.; Tomiyama, Y.; Matsuzawa, Y. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood, 2000, 96(5), 1723-1732.
[http://dx.doi.org/10.1182/blood.V96.5.1723] [PMID: 10961870]
[35]
Ouchi, N.; Shibata, R.; Walsh, K. AMP-activated protein kinase signaling stimulates VEGF expression and angiogenesis in skeletal muscle. Circ. Res., 2005, 96(8), 838-846.
[http://dx.doi.org/10.1161/01.RES.0000163633.10240.3b] [PMID: 15790954]
[36]
Philp, A.J.; Campbell, I.G.; Leet, C.; Vincan, E.; Rockman, S.P.; Whitehead, R.H.; Thomas, R.J.; Phillips, W.A. The phosphatidylinositol 3′-kinase p85alpha gene is an oncogene in human ovarian and colon tumors. Cancer Res., 2001, 61(20), 7426-7429.
[PMID: 11606375]
[37]
Fujisawa, T.; Endo, H.; Tomimoto, A.; Sugiyama, M.; Takahashi, H.; Saito, S.; Inamori, M.; Nakajima, N.; Watanabe, M.; Kubota, N.; Yamauchi, T.; Kadowaki, T.; Wada, K.; Nakagama, H.; Nakajima, A. Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition. Gut, 2008, 57(11), 1531-1538.
[http://dx.doi.org/10.1136/gut.2008.159293] [PMID: 18676419]
[38]
Nigro, E.; Scudiero, O.; Sarnataro, D.; Mazzarella, G.; Sofia, M.; Bianco, A.; Daniele, A. Adiponectin affects lung epithelial A549 cell viability counteracting TNFa and IL-1ß toxicity through AdipoR1. Int. J. Biochem. Cell Biol., 2013, 45(6), 1145-1153.
[http://dx.doi.org/10.1016/j.biocel.2013.03.003] [PMID: 23500159]
[39]
Medina, E.A.; Oberheu, K.; Polusani, S.R.; Ortega, V.; Velagaleti, G.V.N.; Oyajobi, B.O. PKA/AMPK signaling in relation to adiponectin’s antiproliferative effect on multiple myeloma cells. Leukemia, 2014, 28(10), 2080-2089.
[http://dx.doi.org/10.1038/leu.2014.112] [PMID: 24646889]
[40]
Abdul-Ghafar, J.; Soo Oh, S.; Park, S.M.; Wairagu, P.; Nyung Lee, S.; Jeong, Y.; Eom, M.; Yong, S.J.; Jung, S.H. Expression of adiponectin receptor 1 is indicative of favorable prognosis in non-small cell lung carcinoma. Tohoku J. Exp. Med., 2013, 229(2), 153-162.
[http://dx.doi.org/10.1620/tjem.229.153] [PMID: 23358237]
[41]
Niu, K.; Asada, M.; Okazaki, T.; Yamanda, S.; Ebihara, T.; Guo, H.; Zhang, D.; Nagatomi, R.; Arai, H.; Kohzuki, M.; Ebihara, S. Adiponectin pathway attenuates malignant mesothelioma cell growth. Am. J. Respir. Cell Mol. Biol., 2012, 46(4), 515-523.
[http://dx.doi.org/10.1165/rcmb.2011-0068OC] [PMID: 22095628]
[42]
Li, W.; Saud, S.M.; Young, M.R.; Chen, G.; Hua, B. Targeting AMPK for cancer prevention and treatment. Oncotarget, 2015, 6(10), 7365-7378.
[http://dx.doi.org/10.18632/oncotarget.3629] [PMID: 25812084]
[43]
Tebbe, C.; Chhina, J.; Dar, S.A.; Sarigiannis, K.; Giri, S.; Munkarah, A.R.; Rattan, R. Metformin limits the adipocyte tumor-promoting effect on ovarian cancer. Oncotarget, 2014, 5(13), 4746-4764.
[http://dx.doi.org/10.18632/oncotarget.2012] [PMID: 24970804]
[44]
Zhang, L.F.; Tan, D.Q.C.; Jeyasekharan, A.D.; Hsieh, W.S.; Ho, A.S.; Ichiyama, K.; Ye, M.; Pang, B.; Ohba, K.; Liu, X.; de Mel, S.; Cuong, B.K.; Chng, W.J.; Ryo, A.; Suzuki, Y.; Yeoh, K.G.; Toan, N.L.; Yamamoto, N. Combination of vaccine-strain measles and mumps virus synergistically kills a wide range of human hematological cancer cells: Special focus on acute myeloid leukemia. Cancer Lett., 2014, 354(2), 272-280.
[http://dx.doi.org/10.1016/j.canlet.2014.08.034] [PMID: 25193462]
[45]
Lu, T.; Li, M.; Zhao, M.; Huang, Y.; Bi, G.; Liang, J.; Chen, Z.; Zheng, Y.; Xi, J.; Lin, Z.; Zhan, C.; Jiang, W.; Wang, Q.; Tan, L. Metformin inhibits human non-small cell lung cancer by regulating AMPK–CEBPB–PDL1 signaling pathway. Cancer Immunol. Immunother., 2022, 71(7), 1733-1746.
[http://dx.doi.org/10.1007/s00262-021-03116-x] [PMID: 34837101]
[46]
Zhang, Z.; Du, J.; Shi, H.; Wang, S.; Yan, Y.; Xu, Q.; Zhou, S.; Zhao, Z.; Mu, Y.; Qian, C.; Zhao, A.Z.; Cao, S.; Li, F. Adiponectin suppresses tumor growth of nasopharyngeal carcinoma through activating AMPK signaling pathway. J. Transl. Med., 2022, 20(1), 89.
[http://dx.doi.org/10.1186/s12967-022-03283-0] [PMID: 35164782]
[47]
Delaigle, A.M.; Jonas, J.C.; Bauche, I.B.; Cornu, O.; Brichard, S.M. Induction of adiponectin in skeletal muscle by inflammatory cytokines: In vivo and in vitro studies. Endocrinology, 2004, 145(12), 5589-5597.
[http://dx.doi.org/10.1210/en.2004-0503] [PMID: 15319349]
[48]
Okada-Iwabu, M.; Yamauchi, T.; Iwabu, M.; Honma, T.; Hamagami, K.; Matsuda, K.; Yamaguchi, M.; Tanabe, H.; Kimura-Someya, T.; Shirouzu, M.; Ogata, H.; Tokuyama, K.; Ueki, K.; Nagano, T.; Tanaka, A.; Yokoyama, S.; Kadowaki, T. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature, 2013, 503(7477), 493-499.
[http://dx.doi.org/10.1038/nature12656] [PMID: 24172895]
[49]
O’Dell, M.R.; Li Huang, J.; Whitney-Miller, C.L.; Deshpande, V.; Rothberg, P.; Grose, V.; Rossi, R.M.; Zhu, A.X.; Land, H.; Bardeesy, N.; Hezel, A.F. Kras(G12D) and p53 mutation cause primary intrahepatic cholangiocarcinoma. Cancer Res., 2012, 72(6), 1557-1567.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-3596] [PMID: 22266220]
[50]
Nguyen, M.L.T.; Bui, K.C.; Scholta, T.; Xing, J.; Bhuria, V.; Sipos, B.; Wilkens, L.; Nguyen Linh, T.; Velavan, T.P.; Bozko, P.; Plentz, R.R. Targeting interleukin 6 signaling by monoclonal antibody siltuximab on cholangiocarcinoma. J. Gastroenterol. Hepatol., 2021, 36(5), 1334-1345.
[http://dx.doi.org/10.1111/jgh.15307] [PMID: 33091158]
[51]
Bui, K.C.; Barat, S.; Chen, X.; Bozko, P.; Scholta, T.; Nguyen, M.L.T.; Bhuria, V.; Xing, J.; Nguyen, L.T.; Le, H.S.; Velavan, T.P.; Sipos, B.; Wilkens, L.; Malek, N.P.; Plentz, R.R. Silencing of Kangai 1 C-terminal interacting tetraspanin suppresses progression of cholangiocarcinoma. Exp. Cell Res., 2018, 364(1), 59-67.
[http://dx.doi.org/10.1016/j.yexcr.2018.01.028] [PMID: 29366806]
[52]
Chen, X.; Bui, K.C.; Barat, S.; Thi Nguyen, M.L.; Bozko, P.; Sipos, B.; Kalesse, M.; Malek, N.P.; Plentz, R.R. Therapeutic effects of Argyrin F in pancreatic adenocarcinoma. Cancer Lett., 2017, 399, 20-28.
[http://dx.doi.org/10.1016/j.canlet.2017.04.003] [PMID: 28408354]
[53]
Kishore, J.; Goel, M.K.; Khanna, P. Understanding survival analysis: Kaplan-Meier estimate. Int. J. Ayurveda Res., 2010, 1(4), 274-278.
[http://dx.doi.org/10.4103/0974-7788.76794] [PMID: 21455458]
[54]
Rich, J.T.; Neely, J.G.; Paniello, R.C.; Voelker, C.C.J.; Nussenbaum, B.; Wang, E.W. A practical guide to understanding Kaplan-Meier curves. Otolaryngol. Head Neck Surg., 2010, 143(3), 331-336.
[http://dx.doi.org/10.1016/j.otohns.2010.05.007] [PMID: 20723767]
[55]
Kadowaki, T.; Yamauchi, T.; Kubota, N.; Hara, K.; Ueki, K.; Tobe, K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J. Clin. Invest., 2006, 116(7), 1784-1792.
[http://dx.doi.org/10.1172/JCI29126] [PMID: 16823476]
[56]
Faubert, B.; Vincent, E.E.; Poffenberger, M.C.; Jones, R.G. The AMP-activated protein kinase (AMPK) and cancer: Many faces of a metabolic regulator. Cancer Lett., 2015, 356(2), 165-170.
[http://dx.doi.org/10.1016/j.canlet.2014.01.018] [PMID: 24486219]
[57]
Yu, S.W.; Wang, H.; Poitras, M.F.; Coombs, C.; Bowers, W.J.; Federoff, H.J.; Poirier, G.G.; Dawson, T.M.; Dawson, V.L. Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science, 2002, 297(5579), 259-263.
[http://dx.doi.org/10.1126/science.1072221] [PMID: 12114629]
[58]
Chou, C.C.; Lee, K.H.; Lai, I.L.; Wang, D.; Mo, X.; Kulp, S.K.; Shapiro, C.L.; Chen, C.S. AMPK reverses the mesenchymal phenotype of cancer cells by targeting the Akt-MDM2-Foxo3a signaling axis. Cancer Res., 2014, 74(17), 4783-4795.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-0135] [PMID: 24994714]
[59]
Rattan, R.; Giri, S.; Singh, A.K.; Singh, I. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside inhibits cancer cell proliferation in vitro and in vivo via AMP-activated protein kinase. J. Biol. Chem., 2005, 280(47), 39582-39593.
[http://dx.doi.org/10.1074/jbc.M507443200] [PMID: 16176927]
[60]
Yu, H.; Kortylewski, M.; Pardoll, D. Crosstalk between cancer and immune cells: Role of STAT3 in the tumour microenvironment. Nat. Rev. Immunol., 2007, 7(1), 41-51.
[http://dx.doi.org/10.1038/nri1995] [PMID: 17186030]
[61]
Shaw, R.J.; Lamia, K.A.; Vasquez, D.; Koo, S.H.; Bardeesy, N.; DePinho, R.A.; Montminy, M.; Cantley, L.C. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science, 2005, 310(5754), 1642-1646.
[http://dx.doi.org/10.1126/science.1120781] [PMID: 16308421]
[62]
Metformin and cancer. 2018. Available form: https://clinicaltrials.gov/ct2/results?cond=&term=metformin+and+cancer&cntry=&state=&city=&dist=&Search=Search
[63]
Groenendijk, F.H.; Mellema, W.W.; van der Burg, E.; Schut, E.; Hauptmann, M.; Horlings, H.M.; Willems, S.M.; van den Heuvel, M.M.; Jonkers, J.; Smit, E.F.; Bernards, R. Sorafenib synergizes with metformin in NSCLC through AMPK pathway activation. Int. J. Cancer, 2015, 136(6), 1434-1444.
[http://dx.doi.org/10.1002/ijc.29113] [PMID: 25080865]
[64]
Indraccolo, S.; De Salvo, G.L.; Verza, M.; Caccese, M.; Esposito, G.; Piga, I.; Del Bianco, P.; Pizzi, M.; Gardiman, M.P.; Eoli, M.; Rudà, R.; Brandes, A.A.; Ibrahim, T.; Rizzato, S.; Lolli, I.; Zagonel, V.; Lombardi, G. Phosphorylated acetyl-CoA carboxylase is associated with clinical benefit with regorafenib in relapsed glioblastoma: REGOMA trial biomarker analysis. Clin. Cancer Res., 2020, 26(17), 4478-4484.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-4055] [PMID: 32518098]
[65]
Nickkho-Amiry, M.; McVey, R.; Holland, C. Peroxisome proliferator-activated receptors modulate proliferation and angiogenesis in human endometrial carcinoma. Mol. Cancer Res., 2012, 10(3), 441-453.
[http://dx.doi.org/10.1158/1541-7786.MCR-11-0233] [PMID: 22205725]
[66]
Panigrahy, D.; Kaipainen, A.; Huang, S.; Butterfield, C.E.; Barnés, C.M.; Fannon, M.; Laforme, A.M.; Chaponis, D.M.; Folkman, J.; Kieran, M.W. PPARα agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition. Proc. Natl. Acad. Sci., 2008, 105(3), 985-990.
[http://dx.doi.org/10.1073/pnas.0711281105] [PMID: 18199835]
[67]
Yamasaki, D.; Kawabe, N.; Nakamura, H.; Tachibana, K.; Ishimoto, K.; Tanaka, T.; Aburatani, H.; Sakai, J.; Hamakubo, T.; Kodama, T.; Doi, T. Fenofibrate suppresses growth of the human hepatocellular carcinoma cell via PPARα-independent mechanisms. Eur. J. Cell Biol., 2011, 90(8), 657-664.
[http://dx.doi.org/10.1016/j.ejcb.2011.02.005] [PMID: 21514001]
[68]
Zhou, J.; Zhang, S.; Xue, J.; Avery, J.; Wu, J.; Lind, S.E.; Ding, W.Q. Activation of peroxisome proliferator-activated receptor α (PPARα) suppresses hypoxia-inducible factor-1α (HIF-1α) signaling in cancer cells. J. Biol. Chem., 2012, 287(42), 35161-35169.
[http://dx.doi.org/10.1074/jbc.M112.367367] [PMID: 22932900]
[69]
Thuillier, P.; Anchiraico, G.J.; Nickel, K.P.; Maldve, R.E.; Gimenez-Conti, I.; Muga, S.J.; Liu, K.L.; Fischer, S.M.; Belury, M.A. Activators of peroxisome proliferator-activated receptor-? partially inhibit mouse skin tumor promotion. Mol. Carcinog., 2000, 29(3), 134-142.
[http://dx.doi.org/10.1002/1098-2744(200011)29:3<134::AID-MC2>3.0.CO;2-F] [PMID: 11108658]
[70]
Paul, B.; Lewinska, M.; Andersen, J.B. Lipid alterations in chronic liver disease and liver cancer. JHEP Reports, 2022, 4(6), 100479.
[http://dx.doi.org/10.1016/j.jhepr.2022.100479] [PMID: 35469167]
[71]
Pope, E.D., III; Kimbrough, E.O.; Vemireddy, L.P.; Surapaneni, P.K.; Copland, J.A., III; Mody, K. Aberrant lipid metabolism as a therapeutic target in liver cancer. Expert Opin. Ther. Targets, 2019, 23(6), 473-483.
[http://dx.doi.org/10.1080/14728222.2019.1615883] [PMID: 31076001]
[72]
Satriano, L.; Lewinska, M.; Rodrigues, P.M.; Banales, J.M.; Andersen, J.B. Metabolic rearrangements in primary liver cancers: Cause and consequences. Nat. Rev. Gastroenterol. Hepatol., 2019, 16(12), 748-766.
[http://dx.doi.org/10.1038/s41575-019-0217-8] [PMID: 31666728]
[73]
Khoontawad, J.; Intuyod, K.; Rucksaken, R.; Hongsrichan, N.; Pairojkul, C.; Pinlaor, P.; Boonmars, T.; Wongkham, C.; Jones, A.; Plieskatt, J.; Potriquet, J.; Bethony, J.M.; Mulvenna, J.; Pinlaor, S. Discovering proteins for chemoprevention and chemotherapy by curcumin in liver fluke infection-induced bile duct cancer. PLoS One, 2018, 13(11), e0207405.
[http://dx.doi.org/10.1371/journal.pone.0207405] [PMID: 30440021]
[74]
Dezarn, W.A.; Cessna, J.T.; DeWerd, L.A.; Feng, W.; Gates, V.L.; Halama, J.; Kennedy, A.S.; Nag, S.; Sarfaraz, M.; Sehgal, V.; Selwyn, R.; Stabin, M.G.; Thomadsen, B.R.; Williams, L.E.; Salem, R. Recommendations of the American Association of Physicists in Medicine on dosimetry, imaging, and quality assurance procedures for 90 Y microsphere brachytherapy in the treatment of hepatic malignancies. Med. Phys., 2011, 38(8), 4824-4845.
[http://dx.doi.org/10.1118/1.3608909] [PMID: 21928655]
[75]
Luo, G.; Li, B.; Duan, C.; Cheng, Y.; Xiao, B.; Yao, F.; Wei, M.; Tao, Q.; Feng, C.; Xia, X.; Zhou, H.; Zhao, X.; Dai, R. c-Myc promotes cholangiocarcinoma cells to overcome contact inhibition via the mTOR pathway. Oncol. Rep., 2017, 38(4), 2498-2506.
[http://dx.doi.org/10.3892/or.2017.5913] [PMID: 28849072]
[76]
Pai, S.G.; Carneiro, B.A.; Mota, J.M.; Costa, R.; Leite, C.A.; Barroso-Sousa, R.; Kaplan, J.B.; Chae, Y.K.; Giles, F.J. Wnt/beta-catenin pathway: Modulating anticancer immune response. J. Hematol. Oncol., 2017, 10(1), 101.
[http://dx.doi.org/10.1186/s13045-017-0471-6] [PMID: 28476164]
[77]
Zheng, Y.; Zhou, C.; Yu, X.X.; Wu, C.; Jia, H.L.; Gao, X.M.; Yang, J.M.; Wang, C.Q.; Luo, Q.; Zhu, Y.; Zhang, Y.; Wei, J.W.; Sheng, Y.Y.; Dong, Q.Z.; Qin, L.X. Osteopontin promotes metastasis of intrahepatic cholangiocarcinoma through recruiting MAPK1 and mediating Ser675 phosphorylation of β-Catenin. Cell Death Dis., 2018, 9(2), 179.
[http://dx.doi.org/10.1038/s41419-017-0226-x] [PMID: 29415992]
[78]
Wang, W.; Zhong, W.; Yuan, J.; Yan, C.; Hu, S.; Tong, Y.; Mao, Y.; Hu, T.; Zhang, B.; Song, G. Involvement of Wnt/β-catenin signaling in the mesenchymal stem cells promote metastatic growth and chemoresistance of cholangiocarcinoma. Oncotarget, 2015, 6(39), 42276-42289.
[http://dx.doi.org/10.18632/oncotarget.5514] [PMID: 26474277]
[79]
Boulter, L.; Guest, R.V.; Kendall, T.J.; Wilson, D.H.; Wojtacha, D.; Robson, A.J.; Ridgway, R.A.; Samuel, K.; Van Rooijen, N.; Barry, S.T.; Wigmore, S.J.; Sansom, O.J.; Forbes, S.J. WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited. J. Clin. Invest., 2015, 125(3), 1269-1285.
[http://dx.doi.org/10.1172/JCI76452] [PMID: 25689248]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy