Exploring the mechanism of cisplatin resistance by transcriptome sequencing and reversing the chemoresistance by autophagy inhibition in small cell lung cancer
Exploring the mechanism of cisplatin resistance by transcriptome sequencing and reversing the chemoresistance by autophagy inhibition in small cell lung cancer
复制标题
通过转录组测序探索小细胞肺癌顺铂耐药机制并通过自噬抑制逆转化疗耐药
DOI：
10.1016/j.bbrc.2020.09.023
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发表时间：
2020-12-10
影响因子：
3.1
通讯作者：
Chen, Zhenwen
中科院分区：
文献类型：
--
作者：
Ma, Kaiyan;Li, Shuxin;Chen, Zhenwen
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，特别是在小细胞肺癌中，仍不清楚。采用转录组测序技术，对小细胞肺癌顺铂耐药细胞系H446/CDDP及其亲本细胞系H446的差异表达基因进行分析。基因本体（GO）分析和后续实验表明，H446/CDDP细胞中蛋白质泛素化和自噬功能更加活跃。自噬抑制剂3-甲基腺嘌呤和巴弗洛霉素A1对H446/CDDP细胞有保护作用。此外，通过增加溶酶体的pH值来抑制自噬的抗疟药物也可以增强顺铂诱导的细胞死亡。(C)2020爱思唯尔公司All rights reserved.
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 cisplatinresistant 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. (C) 2020 Elsevier Inc. All rights reserved.