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Synergistic effect of a retinoid X receptor-selective ligand bexarotene and docetaxel in prostate cancer. 2019

Danyang Shen, and Huan Wang, and Qiming Zheng, and Sheng Cheng, and Liwei Xu, and Mingchao Wang, and Gong H Li, and Li Q Xia
Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, People's Republic of China.

OBJECTIVE To explore if bexarotene (BEX) synergistically enhances docetaxel (DTX) cytotoxicity in castration-resistant prostate cancer cell lines. 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. CONCLUSIONS 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.

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