Fas基因转导逆转胃癌耐药细胞的作用及其机制分析

Drug sensitizing effect and related mechanisms of Fas gene transduction on human drug-resis-tant gastric cancer cell SGC7901/VCR

目的 观察Fas基因转导人胃癌耐药细胞SGC790 1/VCR对化疗药物的敏感性 ,并初步探讨其机制。方法 以流式细胞仪检测Fas基因转导和对照胃癌细胞在细胞周期中的分布 ;用MTT实验检查癌细胞对多种药物的敏感性 ;用免疫细胞化学染色法检测胃癌细胞P 糖蛋白 (P gp)和拓扑异构酶II(TopoII)的表达。结果 与胃癌细胞SGC790 1和pBK SGC790 1/VCR相比较 ,Fas SGC790 1/VCR在G2期减少 ,S期增多 ,并出现明显的凋亡峰 ;Fas SGC790 1/VCR对DDP ,MMC和 5 Fu的敏感性增加 ,但对VCR和DOX的敏感性无明显变化 ;SGC790 1,pBK SGC790 1/VCR和Fas SGC790 1/VCRTopoII的表达无明显差别 ;Fas SGC790 1/VCRP gp的表达水平明显低于 pBK SGC790 1/VCR ,仅显示弱阳性。 结论 Fas基因可在一定程度上逆转人胃癌耐药细胞SGC790 1/VCR的多药耐药性 (MDR) ,其涉及的相关机制可能是增强细胞对凋亡诱导剂的敏感性 ,以及降低细胞P

Aim To observe the drug sensitizing effect and related mechanisms of Fas gene transduction on human drugresistant gastric cancer cell SGC7901/VCR. Methods The cell cycle alteration, the sensitivity of gastric cancer cells to several antitumor drugs and expression of Pgp and Topo II in gastric cancer cells were detected by FCM, MTT assay and immunocytochemical staining,respectively. Results By comparing with SGC7901 and pBKSGC7901/VCR,FasSGC7901/VCR cells decrease in the G2 stage and increase in the S stage, and obviously apoptotic peak arisen. Increased sensitivity of FasSGC7901/VCR to DDP, MMC and 5Fu;Topo II expression among SGC7901, pBKSGC7901/VCR and FasSGC7901/VCR had no obvious differences;Pgp expression level in pBKSGC7901/VCR was lower than that in SGC7901. Conclusion Fas gene transduction could reverse the multidrug resistance(MDR)of human drugresistant gastric cancer cell SGC7901/VCR, for which the higher sensitivity to apoptosis and decreased expression of Pgp may be responsible.