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 .