Medicine Clinic D, Experimental Nephrology, University Hospital of Münster, 48149 Münster, Germany.
Int J Mol Sci. 2022 Jan 19;23(3):1090. doi: 10.3390/ijms23031090.
The human organic cation transporter 2 (hOCT2) mediates renal and neuronal cellular cisplatin and oxaliplatin uptake, and therefore plays a significant role in the development of side effects associated with these chemotherapeutic drugs. Autophagy is induced by cisplatin and oxaliplatin treatment and is believed to promote cell survival under stressful conditions. We examined in vitro the role of hOCT2 on autophagy induced by cisplatin and oxaliplatin. We also explored the effect of autophagy on toxicities of these platinum derivatives. Our results indicate that autophagy, measured as LC3 II accumulation and reduction in p62 expression level, is induced in response to cisplatin and oxaliplatin in HEK293-hOCT2 but not in wild-type HEK293 cells. Furthermore, inhibition of autophagy is associated with higher toxicity of platinum derivatives, and starvation was found to offer protection against cisplatin-associated toxicity. In conclusion, activation of autophagy could be a potential strategy to protect against unwanted toxicities induced by treatment with platinum derivatives.
人有机阳离子转运体 2（hOCT2）介导顺铂和奥沙利铂在肾脏和神经元细胞中的摄取，因此在这些化疗药物相关副作用的发展中起着重要作用。自噬是由顺铂和奥沙利铂处理诱导的，据信在应激条件下促进细胞存活。我们在体外研究了 hOCT2 对顺铂和奥沙利铂诱导的自噬的作用。我们还探讨了自噬对这些铂衍生物毒性的影响。我们的结果表明，自噬，如 LC3 II 积累和 p62 表达水平降低，是由顺铂和奥沙利铂在 HEK293-hOCT2 中诱导的，但在野生型 HEK293 细胞中没有诱导。此外，自噬的抑制与铂衍生物毒性的增加有关，并且发现饥饿可提供针对顺铂相关毒性的保护。总之，自噬的激活可能是一种潜在的策略，可以防止铂衍生物治疗引起的不必要的毒性。
