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

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(0.16-33.3μmol/L)for 48 h.Mutagenicity and acute and chronic cytotoxicities were assessed using the MTT,clonogenic,and cytokinesis-block micronucleus assays.Gene expression of BIRC5 and BECN1 was evaluated by reverse transcription-polymerase chain reaction.Results:Cisplatin IC50(0.33μmol/L)increased micronucleus frequency 2.50 times.Cisplatin was also cytotoxic in the 0.6-33.3μmol/L range,with reduced expression of the BIRC5 gene,suggesting induction of apoptosis.Besides reducing the expression of the BIRC5 gene,33.3μmol/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 points to a further investigation of the role of autophagy in cisplatin resistance.