RESUMO
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.