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

Abstract

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 (IC 50 ) 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 associated with DDP resistance. XPC silencing significantly inhibited A549/DDP cell proliferation and increased the induction of apoptosis. In addition, XPC knockdown decreased the expression levels of the Akt/mTOR signaling proteins and the expression of their downstream mediator. The data of the present study revealed that XPC inhibition rescued DDP resistance in lung adenocarcinoma cells, which was dependent on the Akt/mTOR signaling pathway. Collectively, XPC may be considered a new strategy for curing DDP-resistant lung cancer and may improve the efficacy of conventional chemotherapy.

Identification of a Seven-lncRNA Immune Risk Signature and Construction of a Predictive Nomogram for Lung Adenocarcinoma

“…In addition, JAK signaling was involved in the formation of TME by regulating T cell, natural killer (NK), and dendritic cell function (29). Evidence has demonstrated that the mammalian target of rapamycin (mTOR) signaling pathway was associated with metastasis and cisplatin resistance in lung adenocarcinoma (30,31). GO analyses also suggested that the low-risk group was associated with immune-related processes, some of which were negatively regulated, and the results of ESTIMATE analysis showed that the tumor cells in the low-risk group had more immune cell infiltration than those in the highrisk group.…”

<p>Delicaflavone Reverses Cisplatin Resistance via Endoplasmic Reticulum Stress Signaling Pathway in Non-Small Cell Lung Cancer Cells</p>

“…The resistance of lung cancer cells to DDP is a complex process, involving multiple factors and genes, including the mechanisms of the accumulation and deactivation of intracellular drugs, DNA damage repair, autophagy, and apoptosis. [14][15][16][17] Recently more and more research has focused on the mechanism of Delicaflavone in tumors. It exerts antitumor activity by inducing apoptosis and autophagy and Figure 2 Delicaflavone united with DDP regulated lung cancer DDP resistant cells invasion, migration.…”

STRIP2, a member of the striatin‐interacting phosphatase and kinase complex, is implicated in lung adenocarcinoma cell growth and migration

“…Suppression of this pathway is considered a latent antitumor therapy . The Akt/mTOR pathway is a critical pathway for LUAD cell proliferation . Through the Akt/mTOR pathway, xeroderma pigmentosum complementation group C repression rescued cisplatin resistance in LUAD cells .…”

“…The Akt/mTOR pathway is a critical pathway for LUAD cell proliferation . Through the Akt/mTOR pathway, xeroderma pigmentosum complementation group C repression rescued cisplatin resistance in LUAD cells . However, a few articles reported that STRIP2 was involved in the modulation of the Akt/mTOR pathway.…”