三氧化二砷对胃癌耐药细胞P-gp、GST-s表达的抑制

Reversal effect and mechanism of arsenic trioxide on multidrug resistance of gastric carcinoma cells

目的研究三氧化二砷(arsenic trioxide,As2O3)对胃癌细胞多药耐药细胞的P-糖蛋白(p-glucoprotein,P-gp)、谷胱甘肽s转移酶(glutathione-s transferring enzyme,GST-s)抑制作用。方法逐渐递增长春新碱(vincristine,VCR)浓度诱导胃癌细胞株SGC7901产生耐药性SGC7901/VCR。MTT法测定诱导前后VCR、5-氟尿嘧啶(fluorouacil,5-Fu)、表阿霉素等抗癌药对肿瘤细胞的杀伤作用,从而明确SGC7901/VCR是否对多种化疗药物产生耐药—即具有多药耐药性;Western blot测定肿瘤细胞内P-gp、GST-s表达。结果胃癌SGC7901/VCR细胞对VCR、5-Fu、表阿霉素的耐药倍数分别为16.56倍、2.69倍及13.05倍。经As2O3预处理24 h后,VCR、5-Fu、表阿霉素对SGC7901/VCR的耐药倍数显著下降(P<0.05)。SGC7901/VCR在静息时细胞内P-gp、GST-s蛋白表达显著高于SGC7901。而As2O3可使SGC7901/VCR细胞内P-gp、GST-s蛋白表达显著下降。结论三氧化二砷可以抑制P-gp、GST-s蛋白的表达,从而降低细胞的耐药性。

Objective To study the inhibitory effect of arsenic trioxide （As2O3 ） on P-glucoprotein （P- gp） and glutathione-s transferring enzyme（GST-s） in gastric carcinoma cells. Methods The density of vincristine （VCR） was increased gradually to induce the drug resistance of gastric carcinoma cell SGC7901. The effect of As2O3 on multidrug resistance （MDR） was treated, MTT assay was used to determine the lethal effect of anticarcinogens on tumor cells and Western blot assay was applied to determine the expression of P-gp and GST-s in tumor cells. Results The resistance of SGC7901/VCR cells to VCR, fluorouacil, and epirubicin were 16.56, 2.69 and 13.05 times, respectively, more than that of SGC7901 cells. After 24 h precondition with As2O3, recovery index （RI） of vincristine, fluorouacil, and epirubicin decreased significantly （P 〈 0.05 ）. Expressions of P-gp and GST-s in resting SGC7901/VCR cells were significantly higher than that in carcinogen-sensitive SGC7901 cells. As203 decreased the expression of P-gp and GST-s in SGC7901/VCR cells significantly. Conclusion As2O3 can partly reverse drug resistance of SGC7901/VCR cells by depressing the expression of P-gp and GST-s.