School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, PR China.
School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, 100069, PR China.
Biochem Biophys Res Commun. 2020 Dec 10;533(3):474-480. doi: 10.1016/j.bbrc.2020.09.023. Epub 2020 Sep 22.
Cisplatin plays a key role in treating small cell lung cancer (SCLC); however, the rapid development of cisplatin resistance limits its treatment effect. The detailed mechanisms of cisplatin-resistance, particularly in SCLC, remain unclear. We analyzed the differentially expressed genes (DEGs) between cisplatin-resistant small cell lung cancer cell line H446/CDDP and its parental cell line H446, using the transcriptome sequencing technique. Gene ontology (GO) analysis and the subsequent tests demonstrated that the functions of protein ubiquitination and autophagy are more active in the H446/CDDP cells. Autophagy plays a protective role in the H446/CDDP cells by using the autophagy inhibitors, 3-methyladenine and bafilomycin A1. Moreover, antimalarial drugs that inhibit autophagy by increasing the pH of lysosomes can also enhance cisplatin-induced cell death.
顺铂在治疗小细胞肺癌（SCLC）中起着关键作用；然而，顺铂耐药的快速发展限制了其治疗效果。顺铂耐药的详细机制，特别是在 SCLC 中，仍然不清楚。我们使用转录组测序技术分析了顺铂耐药小细胞肺癌细胞系 H446/CDDP 与其亲本细胞系 H446 之间的差异表达基因（DEGs）。基因本体（GO）分析和随后的测试表明，H446/CDDP 细胞中蛋白质泛素化和自噬的功能更为活跃。自噬通过使用自噬抑制剂 3-甲基腺嘌呤和巴弗洛霉素 A1 在 H446/CDDP 细胞中发挥保护作用。此外，通过增加溶酶体 pH 值抑制自噬的抗疟药物也可以增强顺铂诱导的细胞死亡。
