Cisplatin-induced downregulation of SOX1 increases drug resistance by activating autophagy in non-small cell lung cancer cell

• Published in: Biochemical and biophysical research communications Vol. 439; no. 2; pp. 187 - 190
• Main Authors: Li, Ning, Li, Xiaobing, Li, Suyun, Zhou, Suzhen, Zhou, Qingwei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.09.2013
• Subjects: Animals; Antineoplastic Agents - pharmacology; Autophagy - drug effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Cell Line, Tumor; Cisplatin; Cisplatin - pharmacology; DNA Methylation - drug effects; Down-Regulation - drug effects; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic - drug effects; Humans; Hypermethylation; Lung; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Mice; Mice, Nude; Non-small cell lung cancer; Promoter Regions, Genetic - drug effects; SOX1; SOXB1 Transcription Factors - genetics; SOX1; Hypermethylation; Cisplatin; Non-small cell lung cancer
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.08.065

•SOX1 is involved in cisplatin resistance.•Promoter methylation of SOX1 was induced by cisplatin.•Inactivation of SOX1 induces autophagy in lung cancer cells. SOX1 was aberrant methylated in hepatocellular cancer and non-small cell lung cancer (NSCLC). Long-term cisplatin exposure promotes methylation of SOX1 in ovarian cancer cell, suggesting that SOX1 may be involved in cisplatin resistance. Our aim was to test the hypothesis that cisplatin resistance is associated with alteration of SOX1 expression in NSCLC. Expression of levels of SOX1 was examined using RT-PCR in cisplatin resistance cells and parental cells. The level of SOX1 mRNA in cisplatin resistance cells was markedly reduced when compared to parental cells. Promoter methylation of SOX1 was induced in cisplatin resistance cells. We also found that SOX1 silencing enhanced the cisplatin-mediated autophagy in NSCLC. This study shows that inactivation of SOX1 by promoter hypermethylation, at least in part, is responsible for cisplatin resistance in human NSCLC.