Evaluating the cytotoxicity of combination treatment with Trichostatin A and Docetaxel in prostate cancer chemotherapy

doi:10.3877/cma.j.issn.2095-5820.2018.03.004

Abstract

Abstract:

Objective

To investigate the therapeutic efficacy of trichostatin A (TSA) in combination with Docetaxel (DTX) in human prostate cancer chemointervention through studying the cytotoxic effect in vitro, and the possible molecular mechanism.

Methods

Prostate cancer cells DU145 and 22Rv1 were treated with different doses of TSA or DTX respectively. The cytotoxic effect was evaluated by WST-1 assay. The PARP cleavage and level of phosphorylated H2A.X (p-H2A.X) were assessed by Western Blot. The genes expression of tumor suppressive maspin、p21^CIP1/WAF1 and Bax were analyzed by reverse transcription followed by quantitative real-time PCR.

Results

The treatment with either TSA or DTX inhibited cell proliferation of prostate cancer DU145 and 22Rv1 cells with differential drug sensitivity. The cytotoxic effect of TSA on 22Rv1 cell (IC50=0.06 μM) was more significant than on DU145 cell (IC50=0.16 μM). But the cytotoxic effect of DTX on DU145 was more significant than on 22Rv1 cell. Combination treatment of TSA with DTX showed synergistic inhibitory effect on cell proliferation of both cell lines. Both PARP cleavage and p-H2A.X level were increased in DTX-induced cytotoxicity companied with increased expression of maspin and Bax in DU145 cells, and of maspin and p21^CIP1/WAF1 in 22Rv1 cells. Treatment with sub-lethal concentration of TSA (0.1 μM) was able to promote DTX-induced expression of tumor suppressive maspin, p21^CIP1/WAF1 and Bax in these two cell lines with a differential manner.

Conclusion

Treatment with TSA or DTX could inhibit the proliferation of prostate cancer DU145 and 22Rv1 cells. DTX treatment was able to induce apoptotic cell death. The combination treatment approach of TSA with DTX showed synergistic effects on increasing expression of tumor suppressive maspin, p21^CIP1/WAF1 and Bax, which may be differentially indispensible to their cytotoxic effect.

Key words: Prostate cancer, Epigenetic regulation, Chemointervention, Cytotoxicity

Jiajia Jiang, Jingxu Yin, Jiaqian Guo, Xueqi Lian, Sijie Tang, Daguang Ni, Can Huang, Xiaohua Li. Evaluating the cytotoxicity of combination treatment with Trichostatin A and Docetaxel in prostate cancer chemotherapy[J]. Chinese Journal of Clinical Laboratory Management(Electronic Edition), 2018, 06(03): 145-152.

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