Characterization of the nucleotide excision repair pathway and evaluation of compounds for overcoming the cisplatin resistance of non­small cell lung cancer cell lines.

Lung cancer has been reported to be the leading cause of cancer­related mortality worldwide. Cisplatin combination chemotherapy is a standard therapeutic strategy for patients with non­small cell lung cancer (NSCLC) lacking driver mutations. However, the development of cisplatin resistance is a major obstacle to effective cancer treatment. The cellular mechanisms underlying cisplatin resistance have been previously revealed to be multifunctional. Accordingly, mechanistic analysis and the development of novel therapeutic strategies for cisplatin­resistant NSCLC are urgently required. The present study mainly focused on the DNA repair mechanisms in cisplatin­resistant NSCLC cells. Additionally, the effects of an Ecteinascidin (Et) derivative on cisplatin­resistant cell lines were examined, by using a cisplatin­resistant NSCLC cell line subjected to nucleotide excision repair (NER) pathway alterations. The results revealed that xeroderma pigmentosum group F­complementing protein (XPF) mRNA expression was strongly associated with cisplatin resistance in cisplatin­resistant NSCLC cell lines. XPF silencing significantly restored the sensitivity of cisplatin­resistant PC­14/CDDP cells to the drug. A potent anticancer effect of Et was observed in the cisplatin­resistant cell line (PC­14/CDDP), in which the NER pathway was altered. On the whole, these findings revealed that the expression levels of NER pathway­related genes, including XPF, may have potential as biomarkers of cisplatin resistance. It was also suggested that Et may be a very promising compound for the development of novel anticancer drugs for the treatment of cisplatin­resistant lung cancer.