Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, Anhui, China.
Autophagy. 2009 Nov;5(8):1107-17. doi: 10.4161/auto.5.8.9842. Epub 2009 Nov 19.
Autophagy may represent a common cellular response to nanomaterials, and modulation of autophagy holds great promise for improving the efficacy of cancer therapy. Fullerene C60 possesses potent anti-cancer activities, but its considerable toxicity towards normal cells may hinder its practical applications. It has been reported that fullerene C60 induces certain hallmarks of autophagy in cancer cells. Here we show that the water-dispersed nanocrystal of underivatized fullerene C60 (Nano-C60) at noncytotoxic concentrations caused authentic autophagy and sensitized chemotherapeutic killing of both normal and drug-resistant cancer cells in a reactive oxygen species (ROS)-dependent and photo-enhanced fashion. We further demonstrated that the chemosensitization effect of Nano-C60 was autophagy-mediated and required a functional Atg5, a key gene in the autophagy signaling pathway. Our results revealed a novel biological function for Nano-C60 in enhancing the cytotoxic action of chemotherapeutic agents through autophagy modulation and may point to the potential application of Nano-C60 in adjunct chemotherapy.
自噬可能代表了一种细胞对纳米材料的常见反应，而自噬的调节对于提高癌症治疗的疗效具有巨大的潜力。富勒烯 C60 具有很强的抗癌活性，但它对正常细胞的相当大的毒性可能会阻碍其实际应用。据报道，富勒烯 C60 在癌细胞中诱导了某些自噬的特征。在这里，我们表明，未衍生的富勒烯 C60 的水散纳米晶（Nano-C60）在非细胞毒性浓度下引起了真正的自噬，并以活性氧（ROS）依赖和光增强的方式使正常和耐药癌细胞的化疗杀伤更加敏感。我们进一步证明，Nano-C60 的化学增敏作用是自噬介导的，需要自噬信号通路中的关键基因 Atg5 发挥功能。我们的结果揭示了 Nano-C60 通过自噬调节增强化疗药物细胞毒性作用的新生物学功能，并可能表明 Nano-C60 在辅助化疗中的潜在应用。
