標題: Vorinostat enhances the cisplatin-mediated anticancer effects in small cell lung cancer cells
作者: Pan, Chun-Hao
Chang, Ying-Fang
Lee, Ming-Shuo
Wen, B-Chen
Ko, Jen-Chung
Liang, Sheng-Kai
Liang, Mei-Chih
生物科技學系
分子醫學與生物工程研究所
Department of Biological Science and Technology
Institute of Molecular Medicine and Bioengineering
關鍵字: Vorinostat;Cisplatin;SCLC;HDAC inhibitor;Combination therapy
公開日期: 7-十一月-2016
摘要: Background: Vorinostat, a histone deacetylase (HDAC) inhibitor, is a promising agent for cancer therapy. Combining vorinostat with cisplatin may relax the chromatin structure and facilitate the accessibility of cisplatin, thus enhancing its cytotoxicity. Studies have not yet investigated the effects of the combination of vorinostat and cisplatin on small cell lung cancer (SCLC). Methods: We first assessed the efficacy of vorinostat with etoposide/cisplatin (EP; triple combination) and then investigated the effects of cotreatment with vorinostat and cisplatin on H209 and H146 SCLC cell lines. The anticancer effects of various combinations were determined in terms of cell viability, apoptosis, cell cycle distribution, and vorinostat-regulated proteins. We also evaluated the efficacy of vorinostat/cisplatin combination in H209 xenograft nude mice. Results: Our data revealed that the triple combination engendered a significant reduction of cell viability and high apoptotic cell death. In addition, vorinostat combined with cisplatin enhanced cell growth inhibition, induced apoptosis, and promoted cell cycle arrest. We observed that the acetylation levels of histone H3 and a-tubulin were higher in combination treatments than in vorinostat treatment alone. Moreover, vorinostat reduced the expression of thymidylate synthase (TS), and TS remained inhibited after cotreament with cisplatin. Furthermore, an in vivo study revealed that the combination of vorinostat and cisplatin significantly inhibited tumor growth in xenograft nude mice (tumor growth inhibition T/C% = 20.5 %). Conclusions: Combined treatments with vorinostat promote the cytotoxicity of cisplatin and induce the expression of vorinostat-regulated acetyl proteins, eventually enhancing antitumor effects in SCLC cell lines. Triple combinations with a low dosage of cisplatin demonstrate similar therapeutic effects. Such triple combinations, if applied clinically, may reduce the undesired adverse effects of cisplatin. The effects of the combination of vorinostat and cisplatin should be evaluated further before conducting clinical trials for SCLC treatment.
URI: http://dx.doi.org/10.1186/s12885-016-2888-7
http://hdl.handle.net/11536/132821
ISSN: 1471-2407
DOI: 10.1186/s12885-016-2888-7
期刊: BMC CANCER
Volume: 16
起始頁: 0
結束頁: 0
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