The Effect of Quercetin in the Yishen Tongluo Jiedu Recipe on the
Development of Prostate Cancer through the Akt1-related CXCL12/
CXCR4 Pathway

Yu      Ning; Yongrong      Wu; Qing      Zhou; Yongjie      Teng

doi:10.2174/1386207326666230530095355

Abstract

Background: It remains a challenge to effectively treat prostate cancer (PCa) that affects global men's health. It is essential to find a natural alternative drug and explore its antitumor mechanism due to the serious toxic side effects of chemotherapy.

Methods: The targets and signaling pathways were analyzed by network pharmacology and verified by molecular docking and LC-MS. The proliferation, apoptosis, invasion, and migration of DU145 cells were detected by the CCK-8 method, flow cytometry, and Transwell, respectively. The Bcl-2, caspase-3, CXCL12, and CXCR4 expressions and Akt1 phosphorylation were determined by Western blot. Akt1 overexpression was applied to identify the involvement of the Akt1- related CXCL12/CXCR4 pathway in regulating PCa. Nude mouse tumorigenesis was performed to analyze the effect of quercetin on PCa in vivo.

Results: Network pharmacology analysis displayed that quercetin was the main active component of the Yishen Tongluo Jiedu recipe and Akt1 was the therapy target of PCa. LC-MS analysis showed that quercetin existed in the Yishen Tongluo Jiedu recipe, and molecular docking proved that quercetin bound to Akt1. Quercetin inhibited the proliferation of DU145 cells by upregulating caspase-3 and downregulating Bcl-2 expression, promoting apoptosis and reducing invasion and migration abilities. In vivo, quercetin downregulated CXCL12 and CXCR4 expressions and inhibited PCa development by the Akt1-related CXCL12/CXCR4 pathway.

Conclusion: As the active component of the Yishen Tongluo Jiedu recipe, quercetin inhibited PCa development through the Akt1-related CXCL12/CXCR4 pathway. This study provided a new idea for PCa treatment and a theoretical basis for further research.

« Previous Next »

Graphical Abstract

[1]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin.,  2018, 68(6), 394-424.
 [http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]

[2]
Mahal, B.A.; Alshalalfa, M.; Zhao, S.G.; Beltran, H.; Chen, W.S.; Chipidza, F.; Davicioni, E.; Karnes, R.J.; Ku, S.Y.; Lotan, T.L.; Muralidhar, V.; Rebbeck, T.R.; Schaeffer, E.M.; Spratt, D.E.; Feng, F.Y.; Nguyen, P.L. Genomic and clinical characterization of stromal infiltration markers in prostate cancer. Cancer,  2020, 126(7), 1407-1412.
 [http://dx.doi.org/10.1002/cncr.32688] [PMID: 31905251]

[3]
Bartzatt, R. Prostate cancer: Biology, incidence, detection methods, treatment methods, and vaccines. Curr. Top. Med. Chem.,  2020, 20(10), 847-854.
 [http://dx.doi.org/10.2174/1568026620666200224100730] [PMID: 32091336]

[4]
Sun, B.L. Immunotherapy in treatment of metastatic prostate cancer: An approach to circumvent immunosuppressive tumor microenvironment. Prostate,  2021, 81(15), 1125-1134.
 [http://dx.doi.org/10.1002/pros.24213] [PMID: 34435699]

[5]
Xiang, Y.; Guo, Z.; Zhu, P.; Chen, J.; Huang, Y. Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science. Cancer Med.,  2019, 8(5), 1958-1975.
 [http://dx.doi.org/10.1002/cam4.2108] [PMID: 30945475]

[6]
De La Taille, A.; Buttyan, R.; Hayek, O.; Bagiella, E.; Shabsigh, A.; Burchardt, M.; Burchardt, T.; Chopin, D.K.; Katz, A. Herbal therapy PC-SPES: in vitro effects and evaluation of its efficacy in 69 patients with prostate cancer. J. Urol.,  2000, 164(4), 1229-1234.
 [http://dx.doi.org/10.1016/S0022-5347(05)67146-7] [PMID: 10992371]

[7]
Guo, H.; Luo, H.; Yuan, H.; Xia, Y.; Shu, P.; Huang, X.; Lu, Y.; Liu, X.; Keller, E.T.; Sun, D.; Deng, J.; Zhang, J. Litchi seed extracts diminish prostate cancer progression via induction of apoptosis and attenuation of EMT through Akt/GSK-3β signaling. Sci. Rep.,  2017, 7(1), 41656.
 [http://dx.doi.org/10.1038/srep41656] [PMID: 28134352]

[8]
Wong, B.Y.; Nguyen, D.L.; Lin, T.; Wong, H.H.; Cavalcante, A.; Greenberg, N.M.; Hausted, R.P.; Zheng, J. Chinese medicinal herb Scutellaria barbata modulates apoptosis and cell survival in murine and human prostate cancer cells and tumor development in TRAMP mice. Eur. J. Cancer Prev.,  2009, 18(4), 331-341.

[9]
Chan, F.L.; Choi, H.L.; Chen, Z.Y.; Chan, P.S.F.; Huang, Y. Induction of apoptosis in prostate cancer cell lines by a flavonoid, baicalin. Cancer Lett.,  2000, 160(2), 219-228.
 [http://dx.doi.org/10.1016/S0304-3835(00)00591-7] [PMID: 11053652]

[10]
Xiaowen, H.; Yi, S. Triptolide sensitizes TRAIL-induced apoptosis in prostate cancer cells via p53-mediated DR5 up-regulation. Mol. Biol. Rep.,  2012, 39(9), 8763-8770.
 [http://dx.doi.org/10.1007/s11033-012-1737-2] [PMID: 22707197]

[11]
Ding, D.; Xu, S.; Zhang, H.; Zhao, W.; Zhang, X.; Jiang, Y.; Wang, P.; Dai, Z.; Zhang, J. 3-Methyladenine and dexmedetomidine reverse lipopolysaccharide-induced acute lung injury through the inhibition of inflammation and autophagy. Exp. Ther. Med.,  2018, 15(4), 3516-3522.
 [http://dx.doi.org/10.3892/etm.2018.5832] [PMID: 29545877]

[12]
Li, Z.; Feiyue, Z.; Gaofeng, L. Traditional Chinese medicine and lung cancer-From theory to practice. Biomed. Pharmacother.,  2021, 137, 111381.
 [http://dx.doi.org/10.1016/j.biopha.2021.111381] [PMID: 33601147]

[13]
Heinlein, C.A.; Chang, C. Androgen receptor in prostate cancer. Endocr. Rev.,  2004, 25(2), 276-308.
 [http://dx.doi.org/10.1210/er.2002-0032] [PMID: 15082523]

[14]
Lv, H.; Li, Z.; Xie, Z.; Hu, X.; Li, H.; Sun, J.; Chen, X.; Wen, C. Innovated formulation of TCM pangolin scales to develop a nova therapy of rheumatoid arthritis. Biomed. Pharmacother.,  2020, 126, 109872.
 [http://dx.doi.org/10.1016/j.biopha.2020.109872] [PMID: 32151943]

[15]
Xu, X.; Chen, F.; Zhang, L.; Liu, L.; Zhang, C.; Zhang, Z.; Li, W. Exploring the mechanisms of anti-ovarian cancer of Hedyotis diffusa Willd and Scutellaria barbata D. Don through focal adhesion pathway. J. Ethnopharmacol.,  2021, 279, 114343.
 [http://dx.doi.org/10.1016/j.jep.2021.114343] [PMID: 34147618]

[16]
Wu, Z.; Yin, B.; You, F. Molecular mechanism of anti-colorectal cancer effect of Hedyotis diffusa willd and its extracts. Front. Pharmacol.,  2022, 13, 820474.
 [http://dx.doi.org/10.3389/fphar.2022.820474] [PMID: 35721163]

[17]
Wu, L.; Chen, Y.; Chen, M.; Yang, Y.; Che, Z.; Li, Q.; You, X.; Fu, W. Application of network pharmacology and molecular docking to elucidate the potential mechanism of Astragalus–Scorpion against prostate cancer. Andrologia,  2021, 53(9), e14165.
 [http://dx.doi.org/10.1111/and.14165] [PMID: 34185887]

[18]
Jin, D.; Liu, F.; Yu, M.; Zhao, Y.; Yan, G.; Xue, J.; Sun, Y.; Zhao, D.; Li, X.; Qi, W.; Wang, X. Jiedu Tongluo Baoshen formula enhances podocyte autophagy and reduces proteinuria in diabetic kidney disease by inhibiting PI3K/Akt/mTOR signaling pathway. J. Ethnopharmacol.,  2022, 293, 115246.
 [http://dx.doi.org/10.1016/j.jep.2022.115246] [PMID: 35398500]

[19]
Jin, D.; Zhao, Y.; Sun, Y.; Xue, J.; Li, X.; Wang, X. Jiedu Tongluo Baoshen formula enhances renal tubular epithelial cell autophagy to prevent renal fibrosis by activating SIRT1/LKB1/AMPK pathway. Biomed. Pharmacother.,  2023, 160, 114340.
 [http://dx.doi.org/10.1016/j.biopha.2023.114340] [PMID: 36738503]

[20]
Lu, M.K.; Chang, C.C.; Chao, C.H.; Hsu, Y.C. Structural changes, and anti-inflammatory, anti-cancer potential of polysaccharides from multiple processing of Rehmannia glutinosa. Int. J. Biol. Macromol.,  2022, 206, 621-632.
 [http://dx.doi.org/10.1016/j.ijbiomac.2022.02.112] [PMID: 35217089]

[21]
Li, Z.L.; Mi, J.; Lu, L.; Luo, Q.; Liu, X.; Yan, Y.M.; Jin, B.; Cao, Y.L.; Zeng, X.X.; Ran, L.W. The main anthocyanin monomer of Lycium ruthenicum Murray induces apoptosis through the ROS/PTEN/PI3K/Akt/caspase 3 signaling pathway in prostate cancer DU-145 cells. Food Funct.,  2021, 12(4), 1818-1828.
 [http://dx.doi.org/10.1039/D0FO02382E] [PMID: 33527955]

[22]
Choi, Y.J.; Choi, Y.K.; Lee, K.M.; Cho, S.G.; Kang, S.Y.; Ko, S.G. SH003 induces apoptosis of DU145 prostate cancer cells by inhibiting ERK-involved pathway. BMC Complement. Altern. Med.,  2016, 16(1), 507.
 [http://dx.doi.org/10.1186/s12906-016-1490-5] [PMID: 27927199]

[23]
Gong, Y.; Li, Y.; Lu, Y.; Li, L.; Abdolmaleky, H.; Blackburn, G.L.; Zhou, J.R. Bioactive tanshinones in Salvia miltiorrhiza inhibit the growth of prostate cancer cells in vitro and in mice. Int. J. Cancer,  2011, 129(5), 1042-1052.
 [http://dx.doi.org/10.1002/ijc.25678] [PMID: 20848589]

[24]
Al-Rabia, M.W.; Alhakamy, N.A.; Rizg, W.Y.; Alghaith, A.F.; Ahmed, O.A.A.; Fahmy, U.A. Boosting curcumin activity against human prostatic cancer PC3 cells by utilizing scorpion venom conjugated phytosomes as promising functionalized nanovesicles. Drug Deliv.,  2022, 29(1), 807-820.
 [http://dx.doi.org/10.1080/10717544.2022.2048133] [PMID: 35266425]

[25]
Hnit, S.S.T.; Yao, M.; Xie, C.; Ge, G.; Bi, L.; Jin, S.; Jiao, L.; Xu, L.; Long, L.; Nie, H.; Jin, Y.; Rogers, L.; Suchowerska, N.; Wong, M.; Liu, T.; De Souza, P.; Li, Z.; Dong, Q. Transcriptional regulation of G2/M regulatory proteins and perturbation of G2/M Cell cycle transition by a traditional Chinese medicine recipe. J. Ethnopharmacol.,  2020, 251, 112526.
 [http://dx.doi.org/10.1016/j.jep.2019.112526] [PMID: 31893534]

[26]
Chirumbolo, S. The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflamm. Allergy Drug Targets,  2010, 9(4), 263-285.
 [http://dx.doi.org/10.2174/187152810793358741] [PMID: 20887269]

[27]
Tang, S.M.; Deng, X.T.; Zhou, J.; Li, Q.P.; Ge, X.X.; Miao, L. Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects. Biomed. Pharmacother.,  2020, 121, 109604.
 [http://dx.doi.org/10.1016/j.biopha.2019.109604] [PMID: 31733570]

[28]
Casagrande, R.; Georgetti, S.R.; Verri, W.A., Jr; Jabor, J.R.; Santos, A.C.; Fonseca, M.J.V. Evaluation of functional stability of quercetin as a raw material and in different topical formulations by its antilipoperoxidative activity. AAPS PharmSciTech,  2006, 7(1), E64-E71.
 [http://dx.doi.org/10.1208/pt070110] [PMID: 16584140]

[29]
van der Woude, H. Gliszczyńska-Świgło, A.; Struijs, K.; Smeets, A.; Alink, G.M.; Rietjens, I.M.C.M. Biphasic modulation of cell proliferation by quercetin at concentrations physiologically relevant in humans. Cancer Lett.,  2003, 200(1), 41-47.
 [http://dx.doi.org/10.1016/S0304-3835(03)00412-9] [PMID: 14550951]

[30]
Fang, R.; Jing, H.; Chai, Z.; Zhao, G.; Stoll, S.; Ren, F.; Liu, F.; Leng, X. Design and characterization of protein-quercetin bioactive nanoparticles. J. Nanobiotechnology,  2011, 9(1), 19.
 [http://dx.doi.org/10.1186/1477-3155-9-19]

[31]
Yang, F.; Song, L.; Wang, H.; Wang, J.; Xu, Z.; Xing, N. Quercetin in prostate cancer: Chemotherapeutic and chemopreventive effects, mechanisms and clinical application potential (Review). Oncol. Rep.,  2015, 33(6), 2659-2668.
 [http://dx.doi.org/10.3892/or.2015.3886] [PMID: 25845380]

[32]
Wang, Y.; Li, J.; Chen, J.J.; Gao, X.; Huang, Z.; Shen, Q. Multifunctional nanoparticles loading with docetaxel and GDC0941 for reversing multidrug resistance mediated by PI3K/Akt signal pathway. Mol. Pharm.,  2017, 14(4), 1120-1132.
 [http://dx.doi.org/10.1021/acs.molpharmaceut.6b01045] [PMID: 28291364]

[33]
Wen, X.; Zhou, L.; Wu, X.; Li, R.; Wen, J.; Sha, J.; Wen, X. The PI3K AKT pathway in the pathogenesis of prostate cancer. Front. Biosci.,  2016, 21(5), 1084-1091.
 [http://dx.doi.org/10.2741/4443] [PMID: 27100493]

[34]
Arya, M.; Patel, H.R.; McGurk, C.; Tatoud, R.; Klocker, H.; Masters, J.; Williamson, M. The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in prostate cancer metastasis. J. Exp. Ther. Oncol.,  2004, 4(4), 291-303.
 [PMID: 15844659]

[35]
Conley-LaComb, M.K.; Saliganan, A.; Kandagatla, P.; Chen, Y.Q.; Cher, M.L.; Chinni, S.R. PTEN loss mediated Akt activation promotes prostate tumor growth and metastasis via CXCL12/CXCR4 signaling. Mol. Cancer,  2013, 12(1), 85.
 [http://dx.doi.org/10.1186/1476-4598-12-85] [PMID: 23902739]

[36]
Singh, S.; Singh, U.P.; Grizzle, W.E.; Lillard, J.W., Jr CXCL12–CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion. Lab. Invest.,  2004, 84(12), 1666-1676.
 [http://dx.doi.org/10.1038/labinvest.3700181] [PMID: 15467730]

[37]
Taichman, R.S.; Cooper, C.; Keller, E.T.; Pienta, K.J.; Taichman, N.S.; McCauley, L.K. Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone. Cancer Res.,  2002, 62(6), 1832-1837.
 [PMID: 11912162]

[38]
Huang, Z. Li, G.; Zhang, Z.; Gu, R.; Wang, W.; Lai, X.; Cui, Z.K.; Zeng, F.; Xu, S.; Deng, F. β2AR-HIF-1α-CXCL12 signaling of osteoblasts activated by isoproterenol promotes migration and invasion of prostate cancer cells. BMC Cancer,  2019, 19(1), 1142.
 [http://dx.doi.org/10.1186/s12885-019-6301-1] [PMID: 31771535]

[39]
Ward, A.B.; Mir, H.; Kapur, N.; Gales, D.N.; Carriere, P.P.; Singh, S. Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways. World J. Surg. Oncol.,  2018, 16(1), 108.
 [http://dx.doi.org/10.1186/s12957-018-1400-z] [PMID: 29898731]

[40]
J, G.; A, Z.; G, P.; N, P.; J, K.; v, A.; N, K.; v, K. Permanent implantation as brachytherapy technique for prostate carcinoma-review of clinical trials and guidelines. Rev. Recent Clin. Trials,  2012, 7(3), 173-180.
 [http://dx.doi.org/10.2174/157488712802281268] [PMID: 22789145]

[41]
BenAissa, R.; Othman, H.; Villard, C.; Peigneur, S.; Mlayah-Bellalouna, S.; Abdelkafi-Koubaa, Z.; Marrakchi, N.; Essafi-Benkhadir, K.; Tytgat, J.; Luis, J.; Srairi-Abid, N. AaHIV a sodium channel scorpion toxin inhibits the proliferation of DU145 prostate cancer cells. Biochem. Biophys. Res. Commun.,  2020, 521(2), 340-346.
 [http://dx.doi.org/10.1016/j.bbrc.2019.10.115] [PMID: 31668811]

[42]
Fridlender, M.; Kapulnik, Y.; Koltai, H. Plant derived substances with anti-cancer activity: From folklore to practice. Front. Plant Sci.,  2015, 6, 799.
 [http://dx.doi.org/10.3389/fpls.2015.00799] [PMID: 26483815]

[43]
Qu, H.W.; Jin, Y.; Cui, Z.L.; Jin, X.B. MicroRNA-373-3p inhibits prostate cancer progression by targeting AKT1. Eur. Rev. Med. Pharmacol. Sci.,  2018, 22(19), 6252-6259.
 [PMID: 30338790]

[44]
Bartholomeusz, C.; Gonzalez-Angulo, A.M. Targeting the PI3K signaling pathway in cancer therapy. Expert Opin. Ther. Targets,  2012, 16(1), 121-130.
 [http://dx.doi.org/10.1517/14728222.2011.644788] [PMID: 22239433]

[45]
Alva-Ensastegui, J.C.; Palomar-Pardavé, M.; Ramírez-Silva, M.T.; Aparicio-Gutierrez, N. Quercetin displacement caused by sodium dodecyl sulphate on inclusion complex quercetin-beta cyclodextrin in an acid environment. J. Photochem. Photobiol. Chem.,  2023, 436, 114392.
 [http://dx.doi.org/10.1016/j.jphotochem.2022.114392]

[46]
Li, B.; Rui, J.; Ding, X.; Yang, X. Exploring the multicomponent synergy mechanism of Banxia Xiexin Decoction on irritable bowel syndrome by a systems pharmacology strategy. J. Ethnopharmacol.,  2019, 233, 158-168.
 [http://dx.doi.org/10.1016/j.jep.2018.12.033] [PMID: 30590198]

[47]
Lee, D.H.; Szczepanski, M.; Lee, Y.J. Role of Bax in quercetin-induced apoptosis in human prostate cancer cells. Biochem. Pharmacol.,  2008, 75(12), 2345-2355.
 [http://dx.doi.org/10.1016/j.bcp.2008.03.013] [PMID: 18455702]

[48]
Murad, H.A.S.; Alqurashi, T.M.A.; Hussien, M.A. Interactions of selected cardiovascular active natural compounds with CXCR4 and CXCR7 receptors: A molecular docking, molecular dynamics, and pharmacokinetic/toxicity prediction study. BMC Complement. Med. Ther,  2022, 22(1), 35.
 [http://dx.doi.org/10.1186/s12906-021-03488-8] [PMID: 35120520]

[49]
Sharmila, G.; Bhat, F.A.; Arunkumar, R.; Elumalai, P.; Raja Singh, P.; Senthilkumar, K.; Arunakaran, J. Chemopreventive effect of quercetin, a natural dietary flavonoid on prostate cancer in in vivo model. Clin. Nutr.,  2014, 33(4), 718-726.
 [http://dx.doi.org/10.1016/j.clnu.2013.08.011] [PMID: 24080313]

[50]
Zhang, X.; Huang, J.; Yu, C.; Xiang, L.; Li, L.; Shi, D.; Lin, F. Quercetin enhanced paclitaxel therapeutic effects towards pc-3 prostate cancer through ER stress induction and ROS production. OncoTargets Ther.,  2020, 13, 513-523.
 [http://dx.doi.org/10.2147/OTT.S228453] [PMID: 32021294]

[51]
Chandrasekar, A.P.; Cummins, N.W.; Badley, A.D. The role of the BCL-2 family of proteins in HIV-1 pathogenesis and persistence. Clin. Microbiol. Rev.,  2019, 33(1), e00107-e00119.
 [http://dx.doi.org/10.1128/CMR.00107-19] [PMID: 31666279]

[52]
Nichani, K.; Li, J.; Suzuki, M.; Houston, J.P. Evaluation of caspase‐3 activity during apoptosis with fluorescence lifetime‐based cytometry measurements and phasor analyses. Cytometry A,  2020, 97(12), 1265-1275.
 [http://dx.doi.org/10.1002/cyto.a.24207] [PMID: 32790129]

[53]
Senthilkumar, K.; Arunkumar, R.; Elumalai, P.; Sharmila, G.; Gunadharini, D.N.; Banudevi, S.; Krishnamoorthy, G.; Benson, C.S.; Arunakaran, J. Quercetin inhibits invasion, migration and signalling molecules involved in cell survival and proliferation of prostate cancer cell line (PC-3). Cell Biochem. Funct.,  2011, 29(2), 87-95.
 [http://dx.doi.org/10.1002/cbf.1725] [PMID: 21308698]

[54]
Tang, S.N.; Singh, C.; Nall, D.; Meeker, D.; Shankar, S.; Srivastava, R.K. The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition. J. Mol. Signal.,  2010, 5, 14.
 [http://dx.doi.org/10.1186/1750-2187-5-14] [PMID: 20718984]

[55]
Bhat, F.A.; Sharmila, G.; Balakrishnan, S.; Arunkumar, R.; Elumalai, P.; Suganya, S.; Raja Singh, P.; Srinivasan, N.; Arunakaran, J. Quercetin reverses EGF-induced epithelial to mesenchymal transition and invasiveness in prostate cancer (PC-3) cell line via EGFR/PI3K/Akt pathway. J. Nutr. Biochem.,  2014, 25(11), 1132-1139.
 [http://dx.doi.org/10.1016/j.jnutbio.2014.06.008] [PMID: 25150162]

[56]
Sun, Y.X.; Wang, J.; Shelburne, C.E.; Lopatin, D.E.; Chinnaiyan, A.M.; Rubin, M.A.; Pienta, K.J.; Taichman, R.S. Expression of CXCR4 and CXCL12 (SDF-1) in human prostate cancers (PCa) in vivo. J. Cell. Biochem.,  2003, 89(3), 462-473.
 [http://dx.doi.org/10.1002/jcb.10522] [PMID: 12761880]

[57]
Conley-LaComb, M.K.; Semaan, L.; Singareddy, R.; Li, Y.; Heath, E.I.; Kim, S.; Cher, M.L.; Chinni, S.R. Pharmacological targeting of CXCL12/CXCR4 signaling in prostate cancer bone metastasis. Mol. Cancer,  2016, 15(1), 68.
 [http://dx.doi.org/10.1186/s12943-016-0552-0] [PMID: 27809841]

[58]
Zhou, W.; Guo, S.; Liu, M.; Burow, M.E.; Wang, G. Targeting CXCL12/CXCR4 axis in tumor immunotherapy. Curr. Med. Chem.,  2019, 26(17), 3026-3041.
 [http://dx.doi.org/10.2174/0929867324666170830111531] [PMID: 28875842]

[59]
Morgan, T.; Koreckij, T.; Corey, E. Targeted therapy for advanced prostate cancer: Inhibition of the PI3K/Akt/mTOR pathway. Curr. Cancer Drug Targets,  2009, 9(2), 237-249.
 [http://dx.doi.org/10.2174/156800909787580999] [PMID: 19275762]

Rights & Permissions Print Cite

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/1386207326666230530095355	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402

Combinatorial Chemistry & High Throughput Screening

The Effect of Quercetin in the Yishen Tongluo Jiedu Recipe on the Development of Prostate Cancer through the Akt1-related CXCL12/ CXCR4 Pathway

Abstract Play Pause

Graphical Abstract

Related Journals

Abstract