XPC inhibition rescues cisplatin resistance via the Akt/mTOR signaling pathway in A549/DDP lung adenocarcinoma cells

作者：Teng Xue, Xiaofan Fan, Qi Li, Shuang Liu, Dongyuan Wu, Shu‐Ya Wang, Yuanqi Shi, Mei Dong · 发表于：Oncology Reports · 年份：2019 · DOI：10.3892/or.2019.6959 · 被引用次数：33 · 研究领域：DNA Repair Mechanisms、Carcinogens and Genotoxicity Assessment、Genetic factors in colorectal cancer

Xeroderma pigmentosum, complementation group C (XPC) is an accessory recognition gene involved in the nucleotide excision repair (NER) pathway, which is activated during the initial DNA damage recognition stage. It participates in the regulation of DNA damage‑induced proliferation and apoptosis. Emerging evidence demonstrates that upregulation of XPC increases the resistance of several tumor cell types to cytotoxic drugs. In addition, it can predict poor patient outcome for non‑small cell lung cancer (NSCLC). However, the mechanisms linking upregulation of XPC and drug resistance in lung cancer are still unclear. In the present study, we aimed to confirm whether XPC was involved in the reversal of the cisplatin (DDP) resistance in drug‑resistant A549/DDP lung adenocarcinoma cells. RT‑PCR and western blot assays were used to examine XPC mRNA and protein expression levels. Cell viability was assessed by CCK‑8 assay. The knockdown of XPC was achieved in A549/DDP cells using si‑RNA, whereas cell proliferation and apoptosis were assessed by wound healing assay and flow cytometric analysis, respectively. The median inhibitory concentration (IC50) value of DDP was assessed by CCK‑8 assay. Western blot assays were conducted for the examination of caspase‑9/3, Bax and Bcl‑2 protein levels, whereas the activation of the PI3K/Akt/mTOR signaling pathway was investigated in XPC‑knockdown cells. High expression of XPC was noted in A549/DDP cells compared with that in A549 cells, which was a...