摘要
目的:探讨新型组蛋白去乙酰化酶抑制剂LBH589或联合多烯紫杉醇(DTX)对人卵巢癌OVCAR-3细胞增殖和凋亡的影响。方法:采用不同浓度LBH589、DTX或两者联合处理OVCAR-3细胞,用四甲基偶氮唑蓝(MTT)法检测细胞增殖活力,台盼兰、吖啶橙溴化乙啶(AO/EB)双染色法检测细胞凋亡;Western blot检测聚腺苷二磷酸核糖聚合酶(PARP)、caspase-3、caspase-7、bcl-2、bax蛋白水平。结果:LBH589、DTX均能抑制OVCAR-3细胞增殖,诱导凋亡,小剂量LBH589联合DTX作用更强。经Calcusyn软件分析证明两者联合具有明显的协同作用。Western blot检测发现caspsae-3、PARP-85kD剪切蛋白增加,bax表达增加,bcl-2表达减少。caspase-7无明显变化。结论:LBH589、DTX能抑制OVCAR-3细胞增殖,诱导凋亡,两者联合有明显的协同作用。
Objective: This work aimed to investigate the effects of LBH589, a novel histone deacetylase (HDAC) inhibitor, alone or in combination with docetaxel (DTX) on the proliferation and apoptosis of the human ovarian cancer cell line OVCAR-3. Methods: OVCAR-3 cells were treated with LBH589, DTX, or a combination of both at various concentrations. The proliferation confirmed by Calcusyn software analysis. OVCAR-3 cells apparently increased in number in the combination therapy than in either LBH589 or DTX therapy alone. Western blot analysis showed that the expression of cleaved PARP-85KD, caspase-3, and bax increased, whereas bcl-2 was downregulated. Conclusion: LBH589 and DTX in vitro can significantly inhibit the proliferation of human ovarian cancer cell line OVCAR-3 and induce cell apoptosis of these cells. Combined LBH589 and DTX treatment against drug-resistant OVCAR-3 cells resulted in a synergistic effect of increased sensitivity to chemotherapy.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2013年第10期567-570,共4页
Chinese Journal of Clinical Oncology
关键词
LBH589
卵巢癌
多烯学杉醇
联合治疗
凋亡
LBH589 (panobinostat), ovarian cancer, docetaxel (DTX), combination therapy, apoptosis