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14 June 2017 : Clinical Research  

CLDN1 Increases Drug Resistance of Non-Small Cell Lung Cancer by Activating Autophagy via Up-Regulation of ULK1 Phosphorylation

Zhenhuan Zhao1ACEF, Jing Li1ABCE, Yan Jiang2DFG, Wen Xu1CDE, Xin Li1ABE, Weili Jing2BEFG*

DOI: 10.12659/MSM.904177

Med Sci Monit 2017; 23:2906-2916

Abstract

BACKGROUND: The aim of this study was to investigate the expression of CLDN1 in non-small cell lung cancer (NSCLC) and its mechanism of action in cisplatin resistance.

MATERIAL AND METHODS: A total of 55 patients with NSCLC admitted to our hospital between October 2013 and October 2015 were included. NSCLC tissues and tumor-adjacent tissues (≥5 cm from tumor edge) were collected. Among the 55 patients, 37 had adenocarcinoma and 18 had squamous cell carcinoma. Quantitative real-time polymerase chain reaction was used to determine mRNA expression, and protein expression was examined using Western blotting. CCK-8 assay was used to determine cell proliferation and Transwell assay was used to detect migration and invasion of the cells. Confocal microscopy was used to observe autophagosomes.

RESULTS: Increased CLDN1 expression promoted the development and metastasis of NSCLC. CLDN1 expression in A549/CDDP cells was up-regulated at both transcriptional and translational levels. Reduced CLDN1 expression decreased the drug resistance, proliferation, migration, and invasion abilities of A549/CDDP cells. Decreased CLDN1 expression promoted the apoptosis of A549/CDDP cells. CLDN1 enhanced CDDP drug resistance of A549 cells by activating autophagy. CLDN1 promoted the autophagy of A549 cells by up-regulating the phosphorylation level of ULK1.

CONCLUSIONS: The present study demonstrates that expression of CLDN1 in NSCLC is up-regulated and it is correlated with clinicopathological features. CLDN1 activates autophagy through up-regulation of ULK1 phosphorylation and promotes drug resistance of NSCLC cells to CDDP.

Keywords: Claudin-1

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750