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

Danyang Shen; Huan Wang; Qiming Zheng; Sheng Cheng; Liwei Xu; Mingchao Wang; Gong H Li; Li Q Xia

doi:10.2147/OTT.S209307

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

Onco Targets Ther. 2019 Sep 24:12:7877-7886. doi: 10.2147/OTT.S209307. eCollection 2019.

Authors

Danyang Shen¹, Huan Wang¹, Qiming Zheng¹, Sheng Cheng¹, Liwei Xu¹, Mingchao Wang¹, Gong H Li¹, Li Q Xia¹

Affiliation

¹ Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, People's Republic of China.

Abstract

Purpose: 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: bexarotene; cell cycle arrest; combination therapy; docetaxel; prostate cancer.