Role of 14‐3‐3σ in resistance to cisplatin in non‐small cell lung cancer cells

The efficacies of chemotherapeutic agents are often limited by side effects and acquired drug resistance. We have investigated whether the differential expression pattern of 14-3-3σ affects cisplatin response in non-small cell lung cancer cell lines. Two pairs of parental/cisplatin resistant cell lines (A549/CRA549 and Calu1/CR-Calu1) and clinical lung cancer biopsy samples were analysed for 14-3-3σ expression. Cell viability was assessed by WST assay; and 14-3-3σ expression was suppressed by siRNA transfection. 14-3-3σ mRNA expression increased in CR-A549 and CR-Calu1 compared with their cisplatin-sensitive parental A549 and Calu1 cell lines. But when 14-3-3σ expression was suppressed, elevated cisplatin response was seen in A549 and CR-Calu1 cell lines. Increased 14-3-3σ expression might also account for reduced cisplatin response in vivo, since, 14-3-3σ expression in clinical biopsy samples obtained from lung cancer patients undergoing cisplatin-based chemotherapy significantly higher in the non-responder compared with the responder group. We therefore propose that increased 14-3-3σ expression is correlated with cisplatin response in non-small cell lung cancer cells; monitoring its expression might become useful in the future in predicting poor outcome to cisplatin treatment and/or the verification of acquired cisplatin resistance in lung cancer patients.