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曲古菌素A和硼替佐米诱导卵巢癌细胞凋亡的协同作用[J]. 肿瘤防治研究, 2010, 37(08): 889-893. DOI: 10.3971/j.issn.1000-8578.2010.08.009
引用本文: 曲古菌素A和硼替佐米诱导卵巢癌细胞凋亡的协同作用[J]. 肿瘤防治研究, 2010, 37(08): 889-893. DOI: 10.3971/j.issn.1000-8578.2010.08.009
TSA and PS-341 Synergistically Induce Apoptosis in Ovarian Cancer Cells[J]. Cancer Research on Prevention and Treatment, 2010, 37(08): 889-893. DOI: 10.3971/j.issn.1000-8578.2010.08.009
Citation: TSA and PS-341 Synergistically Induce Apoptosis in Ovarian Cancer Cells[J]. Cancer Research on Prevention and Treatment, 2010, 37(08): 889-893. DOI: 10.3971/j.issn.1000-8578.2010.08.009

曲古菌素A和硼替佐米诱导卵巢癌细胞凋亡的协同作用

TSA and PS-341 Synergistically Induce Apoptosis in Ovarian Cancer Cells

  • 摘要: 目的:探讨组蛋白去乙酰化酶抑制剂曲古菌素A与蛋白酶体抑制剂硼替佐米单独及联合应用对人卵巢癌细胞株SKOV3存活率和凋亡率的影响。初步探讨两种药物联合应用对诱导SKOV3 细胞凋亡具有的协同作用。 方法曲古菌素A、硼替佐米单独或者联合应用于卵巢癌细胞后,用四甲基偶氮唑蓝(MTT)比色法测定细胞增殖活性,并计算细胞存活率,Annexin-V/PI法流式细胞仪检测细胞凋亡率,蛋白质免疫印迹法(Western blot)检测相关蛋白表达水平。通过检测Caspases-3的活性及其底物多聚ADP核糖聚合酶(PARP)的表达水平进一步说明不同用药组诱导细胞凋亡的情况。 结果联合用药组诱导的细胞凋亡率和单独用药组比较,差异有统计学意义(P<0.05)。几种凋亡相关蛋白Bcl-2、Mcl-1和Bcl-XL, 在联合用药组的表达显著低于单独用药组。 在相同的时间点,联合用药组Caspase-3的活性和单独用药组比较,差异有统计学意义(P<0.001)。结论:低剂量的曲古菌素A和硼替佐米联合作用人卵巢癌细胞系能诱导凋亡,并且这种作用远远强于相同剂量单独用药引起的凋亡。这两种药物的联合应用可能成为人卵巢癌化疗中的新方案。

     

    Abstract: Objective:To investigate the apoptotic effect exerted on human ovarian cancer cells by both the histone deacetylase inhibitor Trichostatin A(TSA) and the proteasome inhibitor PS-341 and their synergistic effect. Methods:Methyl thiazolyl tetrazolium (MTT) assay was applied to examine the cell viability, Annexin-V/PI apoptosis detection kit was used to determine the apoptosis rate of different groups. Besides, Western blot was introduced to evaluate the expression levels of Bcl-2、Mcl-1 and Bcl-XL. To furtherly evaluate apoptosis in different groups, the activity of Caspase-3 and expression level of PARP was detected. Results:The cell apoptosis rates which were caused by TSA/PS-341 regimen or TSA, PS-341 alone were different(P<0.05). Western blot showed that after the treatment of TSA and PS-341 combination, Bcl-2、Mcl-1 and Bcl-XL were down-regulated. Exposure to TSA/PS-341 induced the activity of Caspase-3 and the expression of PARP after 48 h of treatment, and there were significant differences compared with the treatment of drug alone(P<0.001). Conclusion:Low-dose TSA and PS-341 synergistically induce cytotoxicity in ovarian cancer cells, and the effect was much more significant than single drug treatment groups. TSA/PS-341 regimen may represent a potential novel therapeutic strategy for ovarian cancer.

     

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