OncoTargets and Therapy (2019-09-01)

Synergistic effect of a retinoid X receptor-selective ligand bexarotene and docetaxel in prostate cancer

  • Shen D,
  • Wang H,
  • Zheng Q,
  • Cheng S,
  • Xu L,
  • Wang M,
  • Li GH,
  • Xia LQ

Journal volume & issue
Vol. Volume 12
pp. 7877 – 7886

Abstract

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Danyang Shen, Huan Wang, Qiming Zheng, Sheng Cheng, Liwei Xu, Mingchao Wang, Gong H Li, Li Q Xia Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, People’s Republic of ChinaCorrespondence: Li Q Xia; Gong H LiDepartment of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, People’s Republic of ChinaTel +86 1 375 826 4531; +86 1 358 870 8507Fax +86 05 718 604 4817Email [email protected]; [email protected]: To explore if bexarotene (BEX) synergistically enhances docetaxel (DTX) cytotoxicity in castration-resistant prostate cancer cell lines.Materials and methods: MTT assay was used to measure the cytotoxic effect of DTX and BEX on castration-resistant prostate cancer (CRPC) cell proliferation and the combination index (CI) values calculated to analyze the interaction between DTX and BEX. Flow cytometry and Western blot analysis identified the underlying mechanism for the synergistic effect of BEX and DTX.Results: When mitotic slippage happens, BEX can synergistically strengthen the anti-proliferation of DTX in a way of significantly down-regulating cyclinB1 and CDK1 expression, and then arresting cells in G2 phase.Conclusion: Results from this study showed that BEX-induced G2 arrest and DTX-induced mitotic arrest probably contributed to the synergistic effect of BEX and DTX.Keywords: docetaxel, bexarotene, prostate cancer, combination therapy, cell cycle arrest

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