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首页> 外文期刊>World Journal of Gastroenterology >Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells
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Histone deacetylase inhibitor MS-275 alone or combined with bortezomib or sorafenib exhibits strong antiproliferative action in human cholangiocarcinoma cells

机译：组蛋白脱乙酰基酶抑制剂MS-275单独或与硼替佐米或索拉非尼联合使用在人胆管癌细胞中显示出强大的抗增殖作用

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AIM: To investigate the antiproliferative effect of the histone deacetylase (HDAC) inhibitor MS-275 on cholangiocarcinoma cells alone and in combination with conventional cytostatic drugs (gemcitabine or doxorubicin) or the novel anticancer agents sorafenib or bortezomib.rnMETHODS: Two human bile duct adenocarcinoma cell lines (EGI-1 and TFK-1) were studied. Crystal violet staining was used for detection of cell number changes. Cytotoxicity was determined by measuring the release of the cytoplasmic enzyme lactate dehydrogenase (LDH). Apoptosis was determined by measuring the enzyme activity of caspase-3. Cell cycle status reflected by the DNA content was detected by flow cytometry.rnRESULTS: MS-275 treatment potently inhibited the proliferation of EGI-1 and TFK-1 cholangiocarcinoma cells by inducing apoptosis and cell cycle arrest. MS-275-induced apoptosis was characterized by activation of caspase-3, up-regulation of Bax and down-regulation of Bcl-2. Cell cycle was predominantly arrested at the G_1/S checkpoint, which was associated with induction of the cydin-dependent kinase inhibitor p21~(Waf/CIP1). Furthermore, additive anti-neoplastic effects were observed when MS-275 treatment was combined with gemcitabine or doxorubicin, while combination with the multi-kinase inhibitor sorafenib or the proteasome inhibitor bortezomib resulted in overadditive anti-neoplastic effects.rnCONCLUSION: The growth of human cholangiocarcinoma cells can be potently inhibited by MS-275 alone or in combination with conventional cytostatic drugs or new, targeted anticancer agents.
机译：目的：研究组蛋白脱乙酰基酶（HDAC）抑制剂MS-275单独或与常规细胞抑制药物（吉西他滨或阿霉素）或新型抗癌药物索拉非尼或硼替佐米联合使用对胆管癌细胞的增殖作用。方法：两种人胆管腺癌研究了细胞系（EGI-1和TFK-1）。结晶紫染色用于检测细胞数变化。通过测量细胞质酶乳酸脱氢酶（LDH）的释放来确定细胞毒性。通过测量caspase-3的酶活性来确定细胞凋亡。结果：MS-275处理通过诱导细胞凋亡和细胞周期阻滞，有效抑制EGI-1和TFK-1胆管癌细胞的增殖。 MS-275诱导的细胞凋亡的特征在于caspase-3的激活，Bax的上调和Bcl-2的下调。细胞周期主要停留在G_1 / S检查点，这与细胞周期蛋白依赖性激酶抑制剂p21〜（Waf / CIP1）的诱导有关。此外，当MS-275治疗与吉西他滨或阿霉素联用时，观察到了加性抗肿瘤作用，而与多激酶抑制剂索拉非尼或蛋白酶体抑制剂硼替佐米联用则产生了过加性的抗肿瘤作用。结论：人胆管癌的生长。单独或与常规细胞抑制药物或新型靶向抗癌药联合使用，MS-275均可有效抑制细胞。

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