Resistance mechanism to cisplatin in NCI-H460 non-small cell lung cancer cell line: investigating apoptosis, autophagy, and cytogenetic damage

Abstract

Aim: To investigate the effects of cisplatin on the human non-small cell lung carcinoma (NCI-H460) cell line regarding cytotoxicity, genotoxicity, and expression of genes associated with apoptosis (BIRC5) and autophagy (BECN1). Methods: Cell cultures were treated with cisplatin concentrations (0.16-33.3 μmol/L) for 48 h. Mutagenicity and acute and chronic cytotoxicities were assessed using the MTT, clonogenic, and cytokinesis-block micronucleus assays. Gene expression ofBIRC5 andBECN1 was evaluated by reverse transcription-polymerase chain reaction. Results: Cisplatin IC50 (0.33 μmol/L) increased micronucleus frequency 2.50 times. Cisplatin was also cytotoxic in the 0.6-33.3 μmol/L range, with reduced expression of the BIRC5 gene, suggesting induction of apoptosis. Besides reducing the expression of the BIRC5 gene, 33.3 μmol/L cisplatin increased the expression of the BECN1 gene, suggesting that autophagy can be related to cisplatin resistance. Conclusion: Cisplatin inhibited NCI-H460 growth, and cisplatin IC50 induced genotoxic damage. When higher cisplatin concentrations are used, the expression of genes associated with apoptosis and autophagy was changed. This results.