Department of Medical Oncology, Dermatology Hospital, Tongji University, Shanghai 200072, P.R. China.
Department of Medical Oncology, 10th People's Hospital, Tongji University, Shanghai 200072, P.R. China.
Oncol Rep. 2018 Feb;39(2):773-783. doi: 10.3892/or.2017.6115. Epub 2017 Nov 27.
Autophagy is a lysosome-dependent process involved in protein and organelle degradation. It has been suggested that autophagy is activated in nutrient-deficient condition and plays an important role in protecting cells from nutrient shortage. However, the effect of autophagy on chemotherapy during nutrient deficiency has been rarely researched. In the present study, we discovered that hepatocarcinoma cells exhibit chemoinsensitivity accompanied by the activation of autophagy when cultured in nutrient-deprived medium. Inhibition of autophagy by 3-methyladenine or siRNA‑targeted Beclin 1 increased the nutrient deprivation‑induced apoptosis and chemosensitivity in hepatocarcinoma cells. Furthermore, decreased mitochondrial mass was detected when cells underwent autophagy. The present study suggests that induction of autophagy confers a survival advantage for hepatocarcinoma cells during nutrient deprivation, not only rescuing cells from nutrient deficiency-induced cell apoptosis, but also protecting cells from chemotherapy-induced cell death. Combined usage of the inhibition of autophagy and conventional chemotherapeutic agents could be an effective therapy for hepatocarcinoma during nutrient deprivation.
自噬是一种溶酶体依赖性的蛋白和细胞器降解过程。有研究表明，自噬在营养缺乏的条件下被激活，并在保护细胞免受营养缺乏方面发挥重要作用。然而，自噬在营养缺乏时对化疗的影响很少被研究。在本研究中，我们发现肝癌细胞在营养缺乏的培养基中培养时表现出对化疗药物的敏感性增加，同时伴随着自噬的激活。用 3-甲基腺嘌呤或靶向 Beclin 1 的 siRNA 抑制自噬会增加营养剥夺诱导的肝癌细胞凋亡和化疗敏感性。此外，当细胞发生自噬时，线粒体质量会减少。本研究表明，自噬的诱导为肝癌细胞在营养缺乏时提供了生存优势，不仅能挽救细胞免受营养缺乏诱导的细胞凋亡，还能保护细胞免受化疗诱导的细胞死亡。抑制自噬和常规化疗药物的联合使用可能是营养缺乏时治疗肝癌的有效方法。
