Icariside II Enhances Cisplatin-induced Apoptosis by Promoting Endoplasmic Reticulum Stress Signalling in Non-small Cell Lung Cancer Cells

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2022 Mar 28

PMID 35342361

Authors

Zhao Tang

Wenjing Du

Fei Xu

Xianjun Sun

Wenjing Chen

Jie Cui

Weifeng Tang

Fangyong Yang

Fangzhou Teng

Jinpei Lin

Baojun Liu

Jingcheng Dong

Affiliations

Soon will be listed here.

Abstract

Although cisplatin is the most effective first-line drug in the management of advanced non-small cell lung cancer (NSCLC), drug resistance remains a major clinical challenge. There is increasing evidence that icariside II (IS) exhibits antitumour activity in a variety of cancers. In the current study, we investigated the anticancer effects of icariside II combined with cisplatin and elucidated the underlying mechanism in NSCLC. Here, we showed that cotreatment with IS and cisplatin inhibited cell proliferation and induced cellular apoptosis. Using mRNA sequencing (mRNA-seq), we identified differentially expressed genes (DEGs) in which there was an enrichment in PERK-mediated unfolded protein response (UPR) signalling. The western blot results revealed that IS activated endoplasmic reticulum (ER) stress, including three branches of UPR signalling, PERK, IRE1 and ATF6, and the downstream PERK-eIF2α-ATF4-CHOP pathway, thus potentiating the apoptosis induced by cisplatin. In addition, the combination of IS with cisplatin significantly reduced xenograft tumour growth in C57BL/6 and BALB/c nude mice . Notably, the combination therapy displayed no evident toxicity. Taken together, IS enhances cisplatin-induced apoptosis partially by promoting ER stress signalling in NSCLC, suggesting that combination treatment with IS and cisplatin is a novel potential therapeutic strategy for NSCLC.

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