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目的探讨生存素(survivin)与人肺癌多药耐药株 H460/cDDP 获得性耐药的关系。方法采用 RT-PCR、Western 印迹法检测耐药株 H460/cDDP 与敏感株 H460的生存素表达;用针对生存素的小于扰 RNA(siRNA)经脂质体介导转染入耐药株 H460/cDDP,抑制生存素表达;用四甲基偶氮唑盐法(MTT)检测顺铂(DDP)、紫杉醇(Taxol)对耐药株 H460/cDDP 的细胞毒作用。结果耐药株 H460/cDDP 的生存素 mRNA 和蛋白质表达均高于敏感株 H460。生存素 siRNA 转染耐药株 H460/cDDP 后72 h,生存素蛋白质的抑制率为92.3%。耐药株 H460/cDDP 和敏感株 H460对 DDP 的 IC_(50)分别为(6.3±0.6)mg/L、(0.8±0.1)mg/L,对 Taxol 的 IC_(50)分别为(12.7±1.2)mg/L、(1.5±0.3)mg/L;生存素 siRNA 作用后,H460/cDDP 对 DDP、Taxol 的 IC_(50)分别为(4.0±0.9)mg/L(P=0.002)、(8.1±1.7)mg/L(P=0.003)。结论生存素高表达与耐药株 H460/cDDP 的获得性耐药有关,生存素有可能成为逆转肺癌耐药性的有效靶点。
Objective To investigate the relationship between survivin and acquired drug resistance of multidrug-resistant human lung cancer cell line H460 / cDDP. Methods The survivin expression of H460 / cDDP and H460 was detected by RT-PCR and Western blotting. The survivin mRNA was transfected into H460 / cDDP to inhibit the expression of survivin. The cytotoxic effect of cisplatin (DDP) and paclitaxel (Taxol) on the drug-resistant strain H460 / cDDP was detected by MTT assay. Results The survivin mRNA and protein expression of resistant strain H460 / cDDP were higher than that of susceptible strain H460. Survivin siRNA transfected drug-resistant strains H460 / cDDP 72 h, the survivin protein inhibition rate was 92.3%. The IC 50 of drug-resistant strain H460 / cDDP and sensitive strain H460 were (6.3 ± 0.6) mg / L and (0.8 ± 0.1) mg / L respectively, and the IC 50 of Taxol were (12.7 ± 1.2 (4.0 ± 0.9) mg / L (P = 0.002), (8.1), (1.5 ± 0.3) mg / L and (1.5 ± 0.3) mg / ± 1.7) mg / L (P = 0.003). Conclusion The high expression of survivin is associated with the acquired drug resistance of H460 / cDDP. Survivin may be an effective target for reversing the drug resistance of lung cancer.