The Reverse Of Drug Resistance Of The Cisplatin Resistant Cell Line Human Lung Asenocarcinoma (A549/DDP) Induced By GST

Objective:To investigate the reversal effects of the nitric oxide (NO) prodrug JS-K on GST-induced cisplatin resistant cell line A549/DDP. To investigate the impact of JS-K to the expression of GST-πmRNA on A549/DDP and A549 cells. Methods:A549 and A549 /DDP cells were cultured with DDP alone or in combination with JS-K respectively. The inhibition of DDP and the inhibition of DDP in combination with JS-K were assessed with MTT and the IC50 values were calculated. The expression of GST-πmRNA was detected by real-time quantitative reverse transcription-polymerase chain reaction (real-time RT-PCR). Results:The IC 50 value was 1.702±0.100μg/ml,9.943±0.063μg/ml when A549 and A549/DDP cells treated with DDP. The difference between the two groups had no statistical significance (P<0.05). JS-K also has an inhibition effect on both A549 and A549/DDP cells. The difference between the two groups had no statistical significance (P> 0.05).The JS-K IC 10 value was 1.042±0.124μM. Chose JS-K IC10 value as its non-toxic dose. DDP combined with JS-K (0.1μM,0.3μM, 1μM) that bellowed its IC 10 value could significant decrease the IC50 value to 1.963±0.238μg/ml,1.371±0.119μg/ml, 1.083±0.055μg/ml in a concentration dependent manner on A549/DDP cells. The difference compared with blank had statistical significance (P<0.05). The reversal fold was 5.066,7.254,9.178. The GST-πmRNA expression was down regulated after JS-K (0.1μM,0.3μM, 1μM) treated 48h. It induced concentration dependent GST-πmRNA expression changes on A549 and A549/DDP cells. The difference compared with blank had statistical significance (P< 0.05). Conclusion:JS-K can enhance the sensitivity of A549/DDP cells to cisplatin. The reversal effect may be relevant to the down regulation of GST-πmRNA expressions.