三氧化二砷逆转人肺腺癌A549/R细胞耐药及对GSTs表达的影响

Arsenic Trioxide in the Mechanism of Drug Resistance Reversal in A549/R Cell Line of Human Lung Cancer and the Effect on Expression of GSTs

目的探讨三氧化二砷(As2O3)对人肺腺癌A549/R细胞耐药的逆转及谷胱甘肽S-转移酶(GSTs)表达的变化。方法分别采用生化方法及RT-PCR方法检测GSTs活性及GST-πmRNA表达水平的变化。结果0.15μmol/LAs2O3可使A549/R细胞内阿霉素(ADM)浓度增加,其IC50值由原来的0.495μmol/L降低至0.217μmol/L,逆转倍数为2.3倍。耐药细胞中GSTs活性增高,GST-πmRNA呈过表达状态。不同浓度的As2O3作用后,GSTs活性下降(P<0.05),GST-πmRNA表达水平下调,呈浓度依赖性变化。结论As2O3可部分逆转A549/R细胞对ADM的耐药性,GST-π的改变参与其耐药机制。

Objective To investigate the arsenic trioxide in the mechanism of drug resistance reversal in A549/R cell line of human lung cancer and the effect on expression of GSTs . Methods With A549/R cells treated with As2O3 in combination with ADM, the glutathione-s-transferase （GSTs） activity was measured by biochemical method. The expression of GST-πmRNA was assessed by RT-PCR. Results 0. 15 μmol/L As2O3 could significantly increase the intraeellular accumulation of ADM in A549/R cell line （P〈0. 05）. The medium inhibition concentration （IC50） was obviously reduced from 0. 495μmol/L to 0. 217μmol/L, with a reversal ratio of 2.3 as compared to its parental cell line. The GSTs activity in A549/R cell line was higher than in parental cell line A549/S. After 0. 15μmol/L, 0. 375μmol/L As2O3 were given, GSTs activities were decreased （P〈0. 05）. In addition, A549/R cell line had overexpression of GST-πmRNA. A significant down regulation of GST-πmRNA was observed in A549/R cells when As2O3 and ADM were given. Conclusion As2O3 is able to enhance the cytotoxieity of ADM and partly reverse the ADM resistance of A549/R cell line of human lung cancer, which may be related to the variation of GST-π enzyme.