2. Academic Validation
  3. 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

  • Biochem Biophys Res Commun. 2020 Dec 10;533(3):474-480. doi: 10.1016/j.bbrc.2020.09.023.
Kaiyan Ma 1,  Shuxin Li 1,  Xueyun Huo 2,  Meng Guo 2,  Xiaoyan Du 2,  Changlong Li 2,  Xin Liu 2,  Jianyi Lv 3,  Zhenwen Chen 4
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, PR China.
  • 2 School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, 100069, PR China.
  • 3 School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, 100069, PR China. Electronic address: susanvalid@ccmu.edu.cn.
  • 4 School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Cancer Invasion & Metastasis Research, Beijing, 100069, PR China. Electronic address: czwen@ccmu.edu.cn.
PMID: 32977950 DOI: 10.1016/j.bbrc.2020.09.023
Abstract

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.

Keywords

Autophagy; Cisplatin; Resistance; Small cell lung cancer; Transcriptome sequencing; Ubiquitination.

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