TIPE2 suppressed cisplatin resistance by inducing autophagy via mTOR signalling pathway.
Experimental and Molecular Pathology(2020)
Abstract
Tumour necrosis factor-α-induced protein-8-like-2 (TIPE2) has been associated with the progression of numerous cancers. Cisplatin, as a classical chemotherapy strategy for cancers, has been applied in non-small-cell lung cancer (NSCLC) clinical therapy but bears the disadvantage of chemoresistance. The aim of this study was to investigate the role of TIPE2 in cisplatin resistance and illustrate the detailed molecular mechanism. In this study, we proved that TIPE2 was down-regulated in cisplatin (DDP)-resistant NSCLC tissues and DDP-resistant NSCLC cells compared with the sensitive control. The inhibition of TIPE2 contributed to cell cisplatin-resistance, and the overexpression of TIPE2 enhanced cisplatin sensitivity and autophagy. Furthermore, increased TIPE2 elevated apoptosis in DDP-resistant NSCLC cells. In addition, TIPE2 restored the activity of mTOR signalling. Preconditioning with the mTOR activator 3BDO abrogated TIPE2-mediated depression in cisplatin-evoked autophagy. In conclusion, aberrant TIPE2 expression may contribute to the occurrence of chemoresistance by interfering with autophagy in NSCLC in an mTOR-dependent manner. TIPE2 could be used as a novel therapeutic target to overcome cisplatin-resistant NSCLC.
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Key words
cisplatin resistance,autophagy,pathway,tipe2
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