曲古霉素A对SGC7901/ADR细胞系耐药逆转机制的研究

Effect of TSA on the drug-resistance reversion in SGC7901/ADR

目的观察组蛋白去乙酰酶抑制剂曲古霉素A(trichostain,TSA)对体外培养胃癌耐药细胞SGC7901/ADR是否具有逆转耐药的作用,并对其作用机制进行探讨。方法①MTT法计算出胃癌耐药细胞SGC7901/ADR的耐药倍数及TSA作用后的逆转倍数。②分空白组、1.5 nmol/L TSA组和12 nmol/L TSA组,依次作用48 h和72 h,用流式细胞仪检测胃癌耐药细胞内阿霉素(adriacin,ADR)浓度。RT-PCR法检测耐药细胞内MDR1(multidrug resistance)基因表达。结果 TSA对胃癌耐药细胞SGC7901/ADR有明显逆转作用,MTT法计算出SGC7901/ADR细胞的耐药倍数是29.51倍,TSA作用后逆转倍数约为1.95倍,流式细胞仪检测TSA作用后胃癌耐药细胞内阿霉素浓度明显增加,且呈时间剂量依赖性,RT-PCR法检测TSA作用后耐药细胞内MDR1基因表达明显降低。结论 TSA对胃癌耐药细胞SGC7901/ADR具有明显逆转作用,可能是通过下调MDR1的表达,增加细胞内ADR浓度实现的。

Objective To investigate the reversal effect of trichostain A（TSA）,a histone deacetylase inhibitor,in the gastric cancer in vitro,and to explore its mechanism.Methods ①MTT assay was used to calculate the drug-resistance index of the SGC7901/ADR and the reversion drug-resistance index after giving TSA.②The cells were divided into blank group,1.5 nmol/L TSA group,and 12 nmol/L TSA group.The cells were treated respectively for 48 h and 72 h.Then the flow cytometer was used to detect the adriacin（ADR） density in the SGC7901/ADR.RT-PCR was employed to detect the MDR1 gene expression in the SGC7901.Results TSA exerted obvious reversion effects on the SGC7901/ADR.The drug-resistance index obtained by MTT method was 29.51,and the reversion drug-resistance index after giving TSA was 1.95.Flow cytometry results showed that the adriacin density in the SGC7901/ADR obviously increased after giving TSA in a time-and dose-dependent manner.RT-PCR results showed that the MDR1 gene expression in the SGC7901/ADR obviously decreased after giving TSA.Conclusion TSA has a distinct reversion drug-resistance effect on the SGC7901/ADR,which may be implemented by downregulating the MDR1 gene expression and increasing the ADR density in the SGC7901/ADR.