Combination of interferon-α and 5-fluorouracil induces apoptosis through mitochondrial pathway in hepatocellular carcinoma in vitro.
Combination of interferon-α and 5-fluorouracil induces apoptosis through mitochondrial pathway in hepatocellular carcinoma in vitro.
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DOI：
10.1016/j.canlet.2011.02.017
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发表时间：
2011-07
期刊：
影响因子：
9.7
通讯作者：
Haipeng Yin;Fengxiang Xie;Jiao Zhang;Yong-mei Yang;Biping Deng;Jintang Sun;Qing-jie Wang;X. Qu
中科院分区：
文献类型：
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作者：
Haipeng Yin;Fengxiang Xie;Jiao Zhang;Yong-mei Yang;Biping Deng;Jintang Sun;Qing-jie Wang;X. Qu
许多临床报道证明，干扰素- α联合5-氟尿嘧啶治疗晚期肝细胞癌（HCC）非常有效。然而，这种治疗的机制尚不清楚。在这里，我们证明了联合治疗协同抑制fas阴性HCC细胞的生长，阻止细胞周期进展并诱导细胞凋亡。此外，联合治疗显著提高了caspase-8蛋白表达，激活了Bid和细胞色素c，同时抗凋亡基因Bcl-xL的表达在治疗早期明显降低，细胞内钙明显升高。因此，线粒体途径参与了IFN-α/5-FU和Ca2+诱导fas阴性HCC细胞的凋亡，部分促进了对HCC的有益作用。
Many clinical reports have proven that the combination therapy of interferon-alpha plus 5-fluorouracil is remarkably effective for advanced hepatocellular carcinoma (HCC). However, the mechanism of this therapy is not well understood. Here, we demonstrated that the combination therapy synergistically inhibited the growth of Fas-negative HCC cells, arrested cell-cycle progression and induced apoptosis. Moreover, the combination therapy significantly increased the protein expression of caspase-8, activated Bid and cytochrome c. Meanwhile, the expression of anti-apoptotic gene Bcl-xL was reduced and intracellular calcium elevated obviously during the early stage of treatment. Therefore, mitochondrial pathway was involved in the apoptosis of Fas-negative HCC cells induced by IFN-α/5-FU and Ca2+partially promoted the beneficial effect against HCC.