Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
Cancer Res. 2013 Jan 1;73(1):3-7. doi: 10.1158/0008-5472.CAN-12-2464.
Autophagy is a homeostatic cellular recycling system that is responsible for degrading damaged or unnecessary cellular organelles and proteins. Cancer cells are thought to use autophagy as a source of energy in the unfavorable metastatic environment, and a number of clinical trials are now revealing the promising role of chloroquine, an autophagy inhibitor, as a novel antitumor drug. On the other hand, however, the kidneys are highly vulnerable to chemotherapeutic agents. Recent studies have shown that autophagy plays a protective role against acute kidney injury, including cisplatin-induced kidney injury, and thus, we suspect that the use of chloroquine in combination with anticancer drugs may exacerbate kidney damage. Moreover, organs in which autophagy also plays a homeostatic role, such as the neurons, liver, hematopoietic stem cells, and heart, may be sensitive to the combined use of chloroquine and anticancer drugs. Here, we summarize the functions of autophagy in cancer and kidney injury, especially focusing on the use of chloroquine to treat cancer, and address the possible side effects in the combined use of chloroquine and anticancer drugs.
自噬是一种负责降解损伤或不必要的细胞细胞器和蛋白质的细胞内稳态循环系统。癌细胞被认为在不利的转移环境中利用自噬作为能量来源，现在有许多临床试验正在揭示氯喹（一种自噬抑制剂）作为新型抗肿瘤药物的有前途的作用。然而，另一方面，肾脏对化疗药物非常敏感。最近的研究表明，自噬在对抗急性肾损伤（包括顺铂诱导的肾损伤）中发挥保护作用，因此，我们怀疑氯喹与抗癌药物联合使用可能会加重肾脏损伤。此外，自噬也发挥着内稳态作用的器官，如神经元、肝脏、造血干细胞和心脏，可能对氯喹和抗癌药物的联合使用敏感。在这里，我们总结了自噬在癌症和肾损伤中的作用，特别是重点介绍了氯喹治疗癌症的作用，并讨论了氯喹与抗癌药物联合使用可能产生的副作用。
