Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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

Saikosaponin B4 Suppression Cancer Progression by Inhibiting SW480 and SW620 Cells Proliferation via the PI3K/AKT/mTOR Pathway in Colon Cancer

Author(s): Yiwei Zhang, Lizhen Lin, Yushu Wang, Zhenzhen Liu, Wenxin Xia, Hong Sui* and Xueyan Fu*

Volume 22, Issue 11, 2022

Published on: 29 August, 2022

Page: [889 - 903] Pages: 15

DOI: 10.2174/1568009622666220627160834

Price: $65

Abstract

Background: Colon cancer is a gastrointestinal malignancy with high incidence and poor prognosis.

Objective: Saikosaponin B4 (SSB4) is a monomeric component of the Traditional Chinese medicine (TCM), Bupleurum. The current study investigates the therapeutic effect and mechanisms of SSB4 in colon cancer.

Methods: The proliferation of two colon cancer cell lines, SW480 and SW620, were assessed using CCK8 and expression of regulatory molecules, including Bax, Caspase3, Caspase9, Cleaved Caspase3, Cleaved Caspase9 and Bcl2 by flow cytometry and Western blotting.

Results: Survival rates, assessed by CCK8, of SW480 and SW620 cells decreased significantly when the SSB4 concentration was in the range 12.5–50 μg/ml. Flow cytometry measurements indicated apoptosis rates of 55.07% ± 1.63% for SW480 cells and 33.07% ± 1.28% for SW620 cells treated with 25 μg/ml SSB4. Western blotting revealed upregulation of the proapoptotic proteins, Bax, Caspase3, Caspase9, Cleaved Caspase3 and Cleaved Caspase9, and downregulation of the anti-apoptotic protein, Bcl2, in the presence of SSB4. Network pharmacology and molecular docking predicted that the PI3K/Akt/mTOR pathway might be the main regulatory target for the antitumor effect of SSB4. Further Western blotting experiments showed that SSB4 downregulated (p < 0.01) expression of PI3K, Akt, mTOR and the phosphorylated proteins, P-PI3K, P-Akt and P-MTOR. Expression of PI3K, Akt and mTOR mRNA was found to be downregulated by SSB4 (P < 0.01) as the result of RT-PCR measurements.

Conclusion: SSB4 is a potent anti-colon cancer agent. Its effects are likely to be mediated by suppression of the PI3K/AKT/mTOR pathway.

Keywords: Colon cancer, saikosaponin B4, PI3K/AKT/mTOR pathway, apoptosis, PPI network, traditional chinese medicine.

« Previous Next »
Graphical Abstract

[1]
Holm, M.; Saraswat, M.; Joenväärä, S.; Ristimäki, A.; Haglund, C.; Renkonen, R. Colorectal cancer patients with different C-reactive protein levels and 5-year survival times can be differentiated with quantitative serum proteomics. PLoS One, 2018, 13(4), e0195354.
[http://dx.doi.org/10.1371/journal.pone.0195354] [PMID: 29630649]
[2]
Eslami, M.; Yousefi, B.; Kokhaei, P.; Hemati, M.; Nejad, Z.R.; Arabkari, V.; Namdar, A. Importance of probiotics in the prevention and treatment of colorectal cancer. J. Cell. Physiol., 2019, 234(10), 17127-17143.
[http://dx.doi.org/10.1002/jcp.28473] [PMID: 30912128]
[3]
Islami, F.; Ward, E.M.; Sung, H.; Cronin, K.A.; Tangka, F.K.L.; Sherman, R.L.; Zhao, J.; Anderson, R.N.; Henley, S.J.; Yabroff, K.R.; Jemal, A.; Benard, V.B. Annual Report to the Nation on the Status of Cancer, Part 1: National Cancer Statistics. J. Natl. Cancer Inst., 2021, 113(12)
[http://dx.doi.org/10.1093/jnci/djab131] [PMID: 34240195]
[4]
Zhang, J.X.; Yang, Z.R.; Wu, D.D.; Song, J.; Guo, X.F.; Wang, J.; Dong, W.G. Suppressive effect of sinomenine combined with 5-fluorouracil on colon carcinoma cell growth. Asian Pac. J. Cancer Prev., 2014, 15(16), 6737-6743.
[http://dx.doi.org/10.7314/APJCP.2014.15.16.6737] [PMID: 25169518]
[5]
Deng, D. World Cancer Report 2020 comes out-adjusting cancer prevention strategies to adapt to the new trend of cancer epidemic. J Multidisciplinary Cancer Management, 2020, 6(03), 27-32.
[6]
Ashraf-Uz-Zaman, M.; Bhalerao, A.; Mikelis, C.M.; Cucullo, L.; German, N.A. Assessing the current state of lung cancer chemoprevention: a comprehensive overview. Cancers (Basel), 2020, 12(5), 1205-1265.
[http://dx.doi.org/10.3390/cancers12051265] [PMID: 32429547]
[7]
Luo, H.; Vong, C.T.; Chen, H.; Gao, Y.; Lyu, P.; Qiu, L.; Zhao, M.; Liu, Q.; Cheng, Z.; Zou, J.; Yao, P.; Gao, C.; Wei, J.; Ung, C.O.L.; Wang, S.; Zhong, Z.; Wang, Y. Naturally occurring anti-cancer compounds: Shining from Chinese herbal medicine. Chin. Med., 2019, 14(1), 48.
[http://dx.doi.org/10.1186/s13020-019-0270-9] [PMID: 31719837]
[8]
Lam, K.S. New aspects of natural products in drug discovery. Trends Microbiol., 2007, 15(6), 279-289.
[http://dx.doi.org/10.1016/j.tim.2007.04.001] [PMID: 17433686]
[9]
Nair, V.A.; Al-Khayyal, N.A.; Sivaperumal, S.; Abdel-Rahman, W.M. Calponin 3 promotes invasion and drug resistance of colon cancer cells. World J. Gastrointest. Oncol., 2019, 11(11), 971-982.
[http://dx.doi.org/10.4251/wjgo.v11.i11.971] [PMID: 31798778]
[10]
Harvey, A.L. Natural products as a screening resource. Curr. Opin. Chem. Biol., 2007, 11(5), 480-484.
[http://dx.doi.org/10.1016/j.cbpa.2007.08.012] [PMID: 17884696]
[11]
Wu, S-J.; Lin, Y-H.; Chu, C-C.; Tsai, Y-H.; Chao, J.C.J. Curcumin or saikosaponin a improves hepatic antioxidant capacity and protects against Cl4-induced liver injury in rats. J. Med. Food, 2008, 11(2), 224-229.
[http://dx.doi.org/10.1089/jmf.2007.555] [PMID: 18598162]
[12]
Chuan, W.; Gao, A.; Jing, L.; Zhi-Hong, Y.; Wang, Y.; Ji-Guo, Z. The detoxification and synergistic effect of zingiber and pipernigrum composite to radiotherapy and chemotherapy. J TaiShan Med. Coll., 2012, 33(12), 828-832.
[13]
Shilnikova, K.; Piao, M.J.; Kang, K.A.; Fernando, P.; Herath, H.; Cho, S.J.; Hyun, J.W. Natural compound shikonin induces apoptosis and attenuates epithelial to mesenchymal transition in radiation-resistant human colon cancer cells. Biomol. Ther. (Seoul), 2021, 321-365.
[PMID: 34321365]
[14]
Chen, S. Research on the clinical experience of professor jiageng Li in differention and treatment for cancer base on date analyzing and mining. Hubei Univ. Chinese Med, 2018.
[15]
Hsu, Y.L.; Kuo, P.L.; Lin, C.C. The proliferative inhibition and apoptotic mechanism of Saikosaponin D in human non-small cell lung cancer A549 cells. Life Sci., 2004, 75(10), 1231-1242.
[http://dx.doi.org/10.1016/j.lfs.2004.03.008] [PMID: 15219811]
[16]
Wei, Z.; Wang, J.; Shi, M.; Liu, W.; Yang, Z.; Fu, Y. Saikosaponin a inhibits LPS-induced inflammatory response by inducing liver X receptor alpha activation in primary mouse macrophages. Oncotarget, 2016, 7(31), 48995-49007.
[http://dx.doi.org/10.18632/oncotarget.9863] [PMID: 27285988]
[17]
Shin, J.S. Im, H.T.; Lee, K.T. Saikosaponin B2 Suppresses Inflammatory Responses Through IKK/IκBα/NF-κB Signaling Inactivation in LPS-Induced RAW 264.7 Macrophages. Inflammation, 2019, 42(1), 342-353.
[http://dx.doi.org/10.1007/s10753-018-0898-0] [PMID: 30251218]
[18]
Kodama, Y.; Xiaochuan, L.; Tsuchiya, C.; Ohizumi, Y.; Yoshida, M.; Nakahata, N. Dual effect of saikogenin D: In vitro inhibition of prostaglandin E2 production and elevation of intracellular free Ca2+ concentration in C6 rat glioma cells. Planta Med., 2003, 69(8), 765-767.
[http://dx.doi.org/10.1055/s-2003-42795] [PMID: 14531029]
[19]
Hsu, M.J.; Cheng, J.S.; Huang, H.C. Effect of saikosaponin, a triterpene saponin, on apoptosis in lymphocytes: Association with c-myc, p53, and bcl-2 mRNA. Br. J. Pharmacol., 2000, 131(7), 1285-1293.
[http://dx.doi.org/10.1038/sj.bjp.0703559] [PMID: 11090099]
[20]
Jin, X.; Zhang, Y.; Li, Q.; Zhao, J. Mechanisms underlying the beneficial effects of Kaiyu Granule for depression. Neural Regen. Res., 2013, 8(34), 3241-3248.
[PMID: 25206645]
[21]
Ying, Z.L.; Li, X.J.; Dang, H.; Wang, F.; Xu, X.Y. Saikosaponin-d affects the differentiation, maturation and function of monocyte-derived dendritic cells. Exp. Ther. Med., 2014, 7(5), 1354-1358.
[http://dx.doi.org/10.3892/etm.2014.1568] [PMID: 24940438]
[22]
Zhou, X.; Cheng, H.; Xu, D.; Yin, Q.; Cheng, L.; Wang, L.; Song, S.; Zhang, M. Attenuation of neuropathic pain by saikosaponin a in a rat model of chronic constriction injury. Neurochem. Res., 2014, 39(11), 2136-2142.
[http://dx.doi.org/10.1007/s11064-014-1407-y] [PMID: 25107300]
[23]
Li, X.; Ge, J.; Li, Y.; Cai, Y.; Zheng, Q.; Huang, N.; Gu, Y.; Han, Q.; Li, Y.; Sun, R.; Liu, R. Integrative lipidomic and transcriptomic study unravels the therapeutic effects of saikosaponins A and D on non-alcoholic fatty liver disease. Acta Pharm. Sin. B, 2021, 11(11), 3527-3541.
[http://dx.doi.org/10.1016/j.apsb.2021.03.018] [PMID: 34900534]
[24]
Ren, S.; Liu, J.; Xue, Y.; Zhang, M.; Liu, Q.; Xu, J.; Zhang, Z.; Song, R. Comparative permeability of three saikosaponins and corresponding saikogenins in Caco-2 model by a validated UHPLCMS/MS method. J. Pharm. Anal., 2021, 11(4), 435-443.
[http://dx.doi.org/10.1016/j.jpha.2020.06.006] [PMID: 34513119]
[25]
Li, J.; Xie, M. Development of UPLC-MS/MS Method for Determination of Saikosaponin B2 and B4 in Rat Plasma and Application in Pharmacokinetics Study. Chin J Mod Applied Pharmacy, 2019, 36(03), 317-321.
[26]
Maccioni, P.; Lorrai, I.; Fara, F.; Carai, M.A.M.; Gessa, G.L.; Chin, Y.W.; Lee, J.H.; Kwon, H.C.; Corelli, F.; Colombo, G. Differential effects of saikosaponins A, B2, B4, C and D on Alcohol and chocolate self-administration in rats. Alcohol Alcohol., 2020, 55(4), 367-373.
[http://dx.doi.org/10.1093/alcalc/agaa049] [PMID: 32441305]
[27]
Wen-Sheng, W. ERK signaling pathway is involved in p15INK4b/p16INK4a expression and HepG2 growth inhibition triggered by TPA and Saikosaponin a. Oncogene, 2003, 22(7), 955-963.
[http://dx.doi.org/10.1038/sj.onc.1206237] [PMID: 12592382]
[28]
Ye, R.P.; Chen, Z.D.; Saikosaponin, A. An active glycoside from Radix bupleuri, reverses P-glycoprotein-mediated multidrug resistance in MCF-7/ADR cells and HepG2/ADM cells. Xenobiotica, 2017, 47(2), 176-184.
[http://dx.doi.org/10.3109/00498254.2016.1171932] [PMID: 27123551]
[29]
Zhong, D.; Zhang, H.J.; Jiang, Y.D.; Wu, P.; Qi, H.; Cai, C.; Zheng, S.B.; Dang, Q. Saikosaponin-d: A potential chemotherapeutics in castration resistant prostate cancer by suppressing cancer metastases and cancer stem cell phenotypes. Biochem. Biophys. Res. Commun., 2016, 474(4), 722-729.
[http://dx.doi.org/10.1016/j.bbrc.2016.05.017] [PMID: 27155154]
[30]
Wong, V.K.; Li, T.; Law, B.Y.; Ma, E.D.; Yip, N.C.; Michelangeli, F.; Law, C.K.; Zhang, M.M.; Lam, K.Y.; Chan, P.L.; Liu, L. Saikosaponin-d, a novel SERCA inhibitor, induces autophagic cell death in apoptosis-defective cells. Cell Death Dis., 2013, 4(Pt 24), e720.
[http://dx.doi.org/10.1038/cddis.2013.217] [PMID: 23846222]
[31]
Li, R.-f.; Fu, J.-m.; Lyu, X.-z.; Gao, Z.-h.; Wang, H.-w.; Wang, J.-g. Saikosaponins-b suppresses tumor growth and angiogenesis of hepa-tocellular carcinoma by regulating VEGF/ERK/HIF-1α signal pathway. Chin J Pharm Toxicol, 2017, 31(10), 962-963.
[32]
Zong, Z.; Fujikawa-Yamamoto, K.; Ota, T.; Guan, X.; Murakami, M.; Li, A.; Yamaguchi, N.; Tanino, M.; Odashima, S. Saikosaponin b2 induces differentiation without growth inhibition in cultured B16 melanoma cells. Cell Struct. Funct., 1998, 23(5), 265-272.
[http://dx.doi.org/10.1247/csf.23.265] [PMID: 9872567]
[33]
Chen, X.; Liu, C.; Zhao, R.; Zhao, P.; Wu, J.; Zhou, N.; Ying, M. Synergetic and antagonistic molecular effects mediated by the feedback loop of p53 and JNK between saikosaponin D and SP600125 on lung cancer A549 cells. Mol. Pharm., 2018, 15(11), 4974-4984.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00595] [PMID: 30207732]
[34]
Lv, Y.; Hou, X.; Zhang, Q.; Li, R.; Xu, L.; Chen, Y.; Tian, Y.; Sun, R.; Zhang, Z.; Xu, F. Untargeted Metabolomics study of the in vitro anti-hepatoma effect of saikosaponin D in combination with NRP-1 knockdown. Molecules, 2019, 24(7), E1423.
[http://dx.doi.org/10.3390/molecules24071423] [PMID: 30978940]
[35]
Yao, M.; Yang, J.; Cao, L.; Zhang, L.; Qu, S.; Gao, H. Saikosaponin-d inhibits proliferation of DU145 human prostate cancer cells by inducing apoptosis and arresting the cell cycle at G0/G1 phase. Mol. Med. Rep., 2014, 10(1), 365-372.
[http://dx.doi.org/10.3892/mmr.2014.2153] [PMID: 24736800]
[36]
Li, C.; Guan, X.; Xue, H.; Wang, P.; Wang, M.; Gai, X. Reversal of P-glycoprotein-mediated multidrug resistance is induced by saikosaponin D in breast cancer MCF-7/adriamycin cells. Pathol. Res. Pract., 2017, 213(7), 848-853.
[http://dx.doi.org/10.1016/j.prp.2017.01.022] [PMID: 28554760]
[37]
Rebhan, M.; Chalifa-Caspi, V.; Prilusky, J.; Lancet, D. GeneCards: Integrating information about genes, proteins and diseases. Trends Genet., 1997, 13(4), 163-168.
[http://dx.doi.org/10.1016/S0168-9525(97)01103-7] [PMID: 9097728]
[38]
Amberger, J.S.; Hamosh, A. Searching online mendelian inheritance in man (OMIM): a knowledgebase of human genes and genetic phenotypes. Curr. Protoc. Bioinformatics, 2017, 58(1), 2.1-12.
[http://dx.doi.org/10.1002/cpbi.27] [PMID: 28654725]
[39]
Zhou, Y.; Zhang, Y.; Lian, X.; Li, F.; Wang, C.; Zhu, F.; Qiu, Y.; Chen, Y. Therapeutic target database update 2022: Facilitating drug discovery with enriched comparative data of targeted agents. Nucleic Acids Res., 2021, 30(1)
[PMID: 34718717]
[40]
Wishart, D.S.; Feunang, Y.D.; Guo, A.C.; Lo, E.J.; Marcu, A.; Grant, J.R.; Sajed, T.; Johnson, D.; Li, C.; Sayeeda, Z.; Assempour, N.; Iynkkaran, I.; Liu, Y.; Maciejewski, A.; Gale, N.; Wilson, A.; Chin, L.; Cummings, R.; Le, D.; Pon, A.; Knox, C.; Wilson, M. DrugBank 5.0: A major update to the DrugBank database for 2018. Nucleic Acids Res., 2018, 46(D1), D1074-D1082.
[http://dx.doi.org/10.1093/nar/gkx1037] [PMID: 29126136]
[41]
Zhang, X.; Liu, Z.; Chen, S.; Li, H.; Dong, L.; Fu, X. A new discovery: Total Bupleurum saponin extracts can inhibit the proliferation and induce apoptosis of colon cancer cells by regulating the PI3K/Akt/mTOR pathway. J. Ethnopharmacol., 2022, 283, 114742.
[http://dx.doi.org/10.1016/j.jep.2021.114742] [PMID: 34655668]
[42]
Liu, Y.; Yang, S.; Wang, K.; Lu, J.; Bao, X.; Wang, R.; Qiu, Y.; Wang, T.; Yu, H. Cellular senescence and cancer: Focusing on traditional Chinese medicine and natural products. Cell Prolif., 2020, 53(10), e12894.
[http://dx.doi.org/10.1111/cpr.12894] [PMID: 32881115]
[43]
Zhang, Y.; Chen, H.G.; Zhao, C.; Gong, X.J.; Zhou, X. Research progress on antihepatocellular carcinoma mechanism of active ingredients of traditional Chinese medicine. China J. Chin. Mater. Med, 2020, 45(14), 3395-3406.
[44]
Ping, L.; Jian-Ran, H.; Jun, T. Saikosaponin from Bulperum Chinese DC Represses Proliferation and Migration of Gastric Cancer Cell MGC80-3 via Akt/NF-κB Pathway. Chinese J. Cell Biol., 2018, 40(10), 1727-1735.
[45]
Chen, C.H.; Chen, M.F.; Huang, S.J.; Huang, C.Y.; Wang, H.K.; Hsieh, W.C.; Huang, C.H.; Liu, L.F.; Shiu, L.Y. Saikosaponin a induces apoptosis through mitochondria-dependent pathway in hepatic stellate cells. Am. J. Chin. Med., 2017, 45(2), 351-368.
[http://dx.doi.org/10.1142/S0192415X17500227] [PMID: 28231747]
[46]
Tian, Y.D.; Lin, S.; Yang, P.T.; Bai, M.H.; Jin, Y.Y.; Min, W.L.; Ma, H.B.; Wang, B.F. Saikosaponin-d increases the radiosensitivity of hepatoma cells by adjusting cell autophagy. J. Cancer, 2019, 10(20), 4947-4953.
[http://dx.doi.org/10.7150/jca.30286] [PMID: 31598167]
[47]
Lu, M. Effects of Saikosaponin D on apoptosis genes expression profile of the colon cancer cells HT-29. Afr. J. Pharm. Pharmacol., 2013, 7(24), 1640-1644.
[http://dx.doi.org/10.5897/AJPP12.591]
[48]
Zou, Z.; Gao, Z.; Wang, X.; Xi, X. Effect of Curcumin on PI3K/Akt/Bcl-2 Pathway Signaling Lung Adenocarcinoma Cell A549. J. JiangXi Univ. TCM, 2013, 25(05), 15-17.
[49]
Luo, K.W.; Lung, W.Y. Chun-Xie; Luo, X.L.; Huang, W.R. EGCG inhibited bladder cancer T24 and 5637 cell proliferation and migra-tion via PI3K/AKT pathway. Oncotarget, 2018, 9(15), 12261-12272.
[http://dx.doi.org/10.18632/oncotarget.24301] [PMID: 29552308]
[50]
Chen, X.; Wu, Q.; Chen, Y.; Zhang, J.; Li, H.; Yang, Z.; Yang, Y.; Deng, Y.; Zhang, L.; Liu, B. Diosmetin induces apoptosis and enhances the chemotherapeutic efficacy of paclitaxel in non-small cell lung cancer cells via Nrf2 inhibition. Br. J. Pharmacol., 2019, 176(12), 2079-2094.
[http://dx.doi.org/10.1111/bph.14652] [PMID: 30825187]
[51]
Zhu, H.; Zhao, N.; Jiang, M. Isovitexin attenuates tumor growth in human colon cancer cells through the modulation of apoptosis and epithelial-mesenchymal transition via PI3K/Akt/mTOR signaling pathway. Biochem. Cell Biol., 2021, 99(6), 741-749.
[http://dx.doi.org/10.1139/bcb-2021-0045] [PMID: 34219464]
[52]
Chen, G.; Liang, Y.; Liang, X.; Li, Q.; Liu, D. Tanshinone IIA inhibits proliferation and induces apoptosis through the downregulation of survivin in keloid fibroblasts. Ann. Plast. Surg., 2016, 76(2), 180-186.
[http://dx.doi.org/10.1097/SAP.0000000000000544] [PMID: 26101974]
[53]
Vucicevic, K.; Jakovljevic, V.; Colovic, N.; Tosic, N.; Kostic, T.; Glumac, I.; Pavlovic, S.; Karan-Djurasevic, T.; Colovic, M. Association of Bax expression and Bcl2/Bax ratio with clinical and molecular prognostic markers in chronic lymphocytic leukemia. J. Med. Biochem., 2016, 35(2), 150-157.
[http://dx.doi.org/10.1515/jomb-2015-0017] [PMID: 28356875]
[54]
Du, L.; Fei, Z.; Song, S.; Wei, N. Antitumor activity of Lobaplatin against esophageal squamous cell carcinoma through caspase-dependent apoptosis and increasing the Bax/Bcl-2 ratio. Biomed. Pharmacother., 2017, 95, 447-452.
[http://dx.doi.org/10.1016/j.biopha.2017.08.119] [PMID: 28865364]
[55]
Yun, N.; Kim, C.; Cha, H.; Park, W.J.; Shibayama, H.; Park, I.S.; Oh, Y.J. Caspase-3-mediated cleavage of PICOT in apoptosis. Biochem. Biophys. Res. Commun., 2013, 432(3), 533-538.
[http://dx.doi.org/10.1016/j.bbrc.2013.02.017] [PMID: 23415866]
[56]
Li, Q.; Zhang, J.; Liang, Y.; Mu, W.; Hou, X.; Ma, X.; Cao, Q. Tanshinone l exhibits anticancer effects in human endometrial carcinoma HEC-1-A cells via mitochondrial mediated apoptosis, cell cycle arrest and inhibition of JAK/STAT signalling pathway. J. BUON, 2018, 23(4), 1092-1096.
[PMID: 30358216]
[57]
Hu, C.; Cao, Y.; Li, P.; Tang, X.; Yang, M.; Gu, S.; Xiong, K.; Li, T.; Xiao, T. Oleanolic acid induces autophagy and apoptosis via the AMPK-mTOR signaling pathway in colon cancer. J. Oncol., 2021, 2021, 8281718.
[http://dx.doi.org/10.1155/2021/8281718] [PMID: 34326874]
[58]
Yuan, H.; Ma, Q.; Cui, H.; Liu, G.; Zhao, X.; Li, W.; Piao, G. How can synergism of traditional medicines benefit from network pharmacology? Molecules, 2017, 22(7), 61-81.
[http://dx.doi.org/10.3390/molecules22071135] [PMID: 28686181]
[59]
Dong, Y.; Qiu, P.; Zhu, R.; Zhao, L.; Zhang, P.; Wang, Y.; Li, C.; Chai, K.; Shou, D.; Zhao, H. A Combined phytochemistry and network pharmacology approach to reveal the potential antitumor effective substances and mechanism of Phellinus igniarius. Front. Pharmacol., 2019, 10, 266.
[http://dx.doi.org/10.3389/fphar.2019.00266] [PMID: 30941044]
[60]
Turanli, B.; Karagoz, K.; Gulfidan, G.; Sinha, R.; Mardinoglu, A.; Arga, K.Y. A network-based cancer drug discovery: From integrated multi-omics approaches to precision medicine. Curr. Pharm. Des., 2018, 24(32), 3778-3790.
[http://dx.doi.org/10.2174/1381612824666181106095959] [PMID: 30398107]
[61]
Wang, G.; Oh, D.H.; Dassanayake, M. GOMCL: A toolkit to cluster, evaluate, and extract non-redundant associations of Gene Ontology-based functions. BMC Bioinformatics, 2020, 21(1), 139.
[http://dx.doi.org/10.1186/s12859-020-3447-4] [PMID: 32272889]
[62]
Dai, S.; Zhang, G.; Zhao, F.; Shu, Q.; El-Esawi, M.A. Study on the molecular mechanism of the herbal couple Sparganii rhizoma-Curcumae rhizoma in the treatment of lung cancer based on network pharmacology. Evid. Based Complement. Alternat. Med., 2021, 2021, 1-17.
[63]
Saikia, S.; Bordoloi, M. Molecular docking: challenges, advances and its use in drug discovery perspective. Curr. Drug Targets, 2019, 20(5), 501-521.
[http://dx.doi.org/10.2174/1389450119666181022153016] [PMID: 30360733]
[64]
Song, W.; Mei, J.Z.; Zhang, M.; Long Noncoding, R.N.A. Long noncoding RNA PlncRNA-1 promotes colorectal cancer cell progression by regulating the PI3K/Akt signaling pathway. Oncol. Res., 2018, 26(2), 261-268.
[http://dx.doi.org/10.3727/096504017X15031557924132] [PMID: 28835319]
[65]
Sui, H.; Fan, Z.Z.; Li, Q. Signal transduction pathways and transcriptional mechanisms of ABCB1/Pgp-mediated multiple drug resistance in human cancer cells. J. Int. Med. Res., 2012, 40(2), 426-435.
[http://dx.doi.org/10.1177/147323001204000204] [PMID: 22613403]

Rights & Permissions Print Cite
Article Metrics
7
© 2024 Bentham Science Publishers | Privacy Policy