The Enhancement And Mechanism Of Arsenic Trioxide On Chemosensitivity Of Human Breast Cancer MDA-MB-231Cells In Vitro

Purpose:This study aimed to study growth and apoptosis of triple negative breast cancer MDA-MB-231cells in vitro when arsenic trioxide is combined with classical chemotherapyMethods:1) when MDA-MB-231cells are treated with different concentrations of (0.2,0.4,0.6,0.8,1. Oμmol/L) arsenic trioxide for24h、48h、72h, the growth inhibition is detected by thiazolyl blue (MTT) assay, and when the cells are treated for24h, The protein expression of PCNA was detected by Western blotting, then we select the appropriate concentration of arsenic trioxide for the next experiment2) when MDA-MB-231cells are treated with chemotherapy and combined with AS2O3for24h、48h、72h, the growth inhibition is detected by thiazolyl blue (MTT) assay, and when the cells are treated with chemotherapy and combined with AS2O3for24h, the growth inhibition is detected by thiazolyl blue (MTT) assay. the apoptosis was assessed by Annexin V-FITC/PI Apoptosis Detection Kit. The protein expression of PCNA and Caspase-3was detected by Western blottingResults:1) when MDA-MB-231cells are treated with different concentrations (0.2,0.4,0.6,0.8,1.0μmol/L) of arsenic trioxide for24h、48h、72h, the proliferation inhibitory effect of MDA-MB-231cell gradually increase with the rise of arsenic trioxide dose in dose and time dependent manner. And it is most obvious at1.0μmol/L, meanwhile the expression of PCNA levels is decreasing with the rise of arsenic trioxide dose, so we choose1.0μmol/L for the next experiment.2) when MDA-MB-231cells are treated with chemotherapy and combined with AS2O3for24h、48h、72h, the inhibition rate for arsenic trioxide combined with chemotherapy group is highest。when the cells are treated with chemotherapy and combined with AS2O3for24h, and when the arsenic trioxide and the other groups is compared with the control group, the early apoptosis rate is50.52%,25.84%,20.81%,21.14%,20.43% and the apoptosis rate of5groups (arsenic trioxide combined with chemotherapy group) increased significantly compared with the other groups, there is a significant difference (P<0.05), and when arsenic trioxide chemotherapy group (Group5) is compared with the chemotherapy group (group4) and single drug group (Group1, Group2, Group3), the expression of PCNA were significantly different (P<0.05), there is no significant difference (P>0.05) between each single drug, and chemotherapy combined with As2O3also down-regulated the level of the protein expression of PCNA, and elevated the protein expression of Caspase-3more prominently, the expression of the protein were significantly different (P<0.05), but no significant difference (P>0.05) between each single drug。Conclusion:AS2O3can enhance the anti-MDA-MB-231cells effects of chemotherapy, and the molecular mechanism may contribute to down-regulation of PCNA and up-regulation of caspase-3.