Role of autophagy in resistance to oxaliplatin in hepatocellular carcinoma cells
Role of autophagy in resistance to oxaliplatin in hepatocellular carcinoma cells
复制标题
自噬在肝癌细胞奥沙利铂耐药中的作用
DOI：
10.3892/or.2011.1464
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发表时间：
2012-01-01
期刊：
影响因子：
4.2
通讯作者：
Qiu, Weihua
中科院分区：
文献类型：
--
作者：
Du, Hailei;Yang, Weiping;Qiu, Weihua
尽管奥沙利铂最初具有良好的抗肿瘤活性，但基于奥沙利铂的联合治疗最终可导致肿瘤耐药反应。在这项研究中，我们旨在了解自噬在肝癌细胞对奥沙利铂耐药中的作用，并讨论其潜在的治疗意义。我们发现暴露于奥沙利铂可显着增加LC_3的脂化和随后的LC_3点状形成。奥沙利铂抑制肝癌细胞增殖的同时，ATG7干扰抑制自噬和氯喹预处理进一步增加了肝癌细胞对化疗的敏感性。同时，奥沙利铂诱导的细胞凋亡明显增强。这些结果表明，自噬可能在HepG2细胞对奥沙利铂耐药中起重要作用。有趣的是，通过抑制自噬，这种抵抗力可以明显恢复。这也指出了通过干扰自噬来治疗肝癌的潜在方法。
In spite of an initially promising anti-tumor activity, oxaliplatin-based combinatorial treatments can eventually result in a tumor resistance response. In this study we aimed to understand the role of autophagy in HCC cell resistance to oxaliplatin and to discuss its potential therapeutic implication. We found that exposure to oxaliplatin induced a significant increase in LC3 lipidation and subsequent LC3 puncta formation. While the proliferation of HCC cells was inhibited upon oxaliplatin exposure, inhibition of autophagy by ATG7 interference and chloroquine pre-treatment further increased the sensitivity to chemotherapy. Meanwhile, the oxaliplatin-induced apoptotic cell death was significantly enhanced. These results suggest that autophagy may function importantly in HepG2 cell resistance to oxaliplatin. Intriguingly, the resistance could be recovered apparently by inhibition of autophagy. This also points to the potential therapy for hepatoma by perturbing autophagy.