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

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

Received 21 March 2019

Accepted for publication 16 August 2019

Published 24 September 2019 Volume 2019:12 Pages 7877—7886

DOI https://doi.org/10.2147/OTT.S209307

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 1

Editor who approved publication: Professor Gaetano Romano


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 China

Correspondence: Li Q Xia; Gong H Li
Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, People’s Republic of China
Tel +86 1 375 826 4531; +86 1 358 870 8507
Fax +86 05 718 604 4817
Email xialiqun@zju.edu.cn; 3193119@zju.edu.cn

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: docetaxel, bexarotene, prostate cancer, combination therapy, cell cycle arrest


Corrigendum for this paper has been published


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