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

 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／L As2O3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。

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

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 t reated with As₂O₃ in combination with ADM , the glutathione-s-t ransferase ( GSTs) activity was measured by biochemical method. The expression of GST-π mRNA was assessed by RT-PCR. Results 　0. 15μmol/ L As₂O₃ could significantly increase the int racellular accumulation of ADM in A549/ R cell line ( P < 0. 05) . The medium inhibition concent ration ( 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. Af ter 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-π mRNA . A significant down regulation of GST-π mRNA was observed in A549/ R cells whenAs₂O₃ and ADM were given . Conclusion 　As₂O₃ is able to enhance the cytotoxicity 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 .