Histone deacetylase inhibitor, trichostatin a, synergistically enhances paclitaxel-induced cytotoxicity in urothelial carcinoma cells by suppressing the ERK pathway

Fu Shun Hsu, June Tai Wu, Jing Yi Lin, Shao Ping Yang, Kuan Lin Kuo, Wei Chou Lin, Chung Sheng Shi, Po Ming Chow, Shih Ming Liao, Chun I. Pan, Jo Yu Hong, Hong Chiang Chang, Kuo How Huang*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

21 引文 斯高帕斯(Scopus)

摘要

Trichostatin A (TSA), an antifungal antibiotic derived from Streptomyces, inhibits mammalian histone deacetylases, and especially, selectively inhibits class I and II histone deacetylase (HDAC) families of enzymes. TSA reportedly elicits an antiproliferative response in multifarious tumors. This study investigated the antitumor effects of TSA alone and in combination with paclitaxel when applied to two high-grade urothelial carcinoma (UC) cell lines (BFTC-905 and BFTC-909). Fluorescence-activated cell sorting, flow cytometry, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium assay were used to assess TSA’s cytotoxicity and effects on apoptosis induction. TSA induced synergistic cytotoxicity, when combined with paclitaxel (combination index < 1), resulted in concomitant suppression of paclitaxel-induced activation of phospho-extracellular signal-regulated kinase (ERK) 1/2. A xenograft nude mouse model confirmed that TSA enhances the antitumor effects of paclitaxel. These findings demonstrate that the administration of TSA in combination with paclitaxel elicits a synergistic cytotoxic response. The results of this study indicate that the chemoresistance of UC could be circumvented by combining HDAC inhibitors to target the ERK pathway.

原文英語
文章編號1162
期刊International Journal of Molecular Sciences
20
發行號5
DOIs
出版狀態已出版 - 01 03 2019

文獻附註

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© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

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