Reversal effect and mechanism of arsenic trioxide on multidrug resistance of gastric carcinoma cells SGC7901 / 药学学报

ABSTRACT

The purpose of this study is to investigate the reversal effect and its mechanism of arsenic trioxide (As2O3) on multidrug resistance of gastric carcinoma cells. The concentration of vincristine (VCR) increased gradually to induce the drug resistance of gastric carcinoma cell SGC7901. MTT assay was used to determine the lethal effect of anticarcinogens on tumor cells and Western blotting assay was applied to determine the expression of P-glucoprotein (P-gp) and glutathione S-transferase (GST-s) in tumor cells. As a result, the resistance of SGC7901/VCR cells to VCR, fluorouracil and epirubicin was 16.56, 2.69 and 13.05 times, respectively, more than that of SGC7901 cells. After 24 h precondition with As2O3, RI of vincristine, fluorouracil and epirubicin decreased significantly (P < 0.05). Expression of P-gp and GST-s in resting SGC7901/VCR cells was significantly higher than that in carcinogen-sensitive SGC7901 cells. As2O3 decreased the expression of P-gp and GST-s in SGC7901/VCR cells significantly, while it showed no significant effect on carcinogen-sensitive SGC7901 cells. The result suggested that As2O3 could partly reverse drug resistance of SGC7901/VCR cells by probably the mechanism of decreasing the expression of P-gp and GST-s.