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Curcumin increases crizotinib sensitivity through the inactivation of autophagy via epigenetic modulation of the miR-142-5p/Ulk1 axis in non-small cell lung cancer

Authors :
Yu-Zheng He
Shan-Ling Yu
Xiao-Ning Li
Xian-Hua Bai
Hai-Tao Li
Yan-Chao Liu
Bao-Lei Lv
Xiu-Min Zhao
Dong Wei
He-Lin Zhang
Fan-Nian Li
GuoLei Li
Shuai Li
Source :
Cancer biomarkers : section A of Disease markers. 34(2)
Publication Year :
2021

Abstract

Drug resistance is a critical factor responsible for the recurrence of non-small cell lung cancer (NSCLC). Previous studies suggest that curcumin acts as a chemosensitizer and radiosensitizer in human malignancies, but the underlying mechanism remains elusive. In the present study, we explored how curcumin regulates the expression of miR-142-5p and sensitizes NSCLC cells to crizotinib. We found that miR-142-5p is significantly downregulated in NSCLC tissue samples and cell lines. Curcumin could increase crizotinib cytotoxicity by epigenetically restoring the expression of miR-142-5p. Furthermore, curcumin treatment suppressed the expression of DNA methylation-related enzymes, including DNMT1, DNMT3A, and DNMT3B, in NSCLC cells. In addition, the upregulation of miR-142-5p expression increased crizotinib cytotoxicity and induced apoptosis in tumor cells in a similar manner to that of curcumin. Strikingly, miR-142-5p overexpression suppressed crizotinib-induced autophagy in A549 and H460 cells. Mechanistically, miR-142-5p inhibited autophagy in lung cancer cells by targeting Ulk1. Overexpression of Ulk1 abrogated the miR-142-5p-induced elevation of crizotinib cytotoxicity in A549 and H460 cells. Collectively, our findings demonstrate that curcumin sensitizes NSCLC cells to crizotinib by inactivating autophagy through the regulation of miR-142-5p and its target Ulk1.

Details

ISSN :
18758592
Volume :
34
Issue :
2
Database :
OpenAIRE
Journal :
Cancer biomarkers : section A of Disease markers
Accession number :
edsair.doi.dedup.....5ca9a01ce394bc54727bebd444b531d0