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三氧化二砷逆转人胃癌细胞SGC7901/ADR耐药性的作用机制
Reversal mechanism of arsenic trioxide in the drug resistance of human gastric carcinoma SGC7901/ADR cell line
【摘要】 目的:探讨三氧化二砷(As2O3)对胃癌细胞SGC7901/ADR阿霉素(ADM)耐药性的逆转作用及其逆转机制。方法:采用MTT法检测As2O3的非细胞毒性浓度和SGC7901/ADR细胞对ADM的敏感性,用流武细胞仪检测细胞内药物浓度和P-gp功能,免疫组织化学法检测细胞GST-π和TPPOⅡ的表达。结果:0.4~0.8μmol/L As2O3对耐药细胞SGC7901/ ADR无明显毒性,0.8μmol/L的As2O3可抑制P-gp功能,下调GST-π表达,显著提高SGC7901/ADR细胞内ADM浓度,增加SGC7901/ADR细胞对ADM的敏感性。结论:As2O3可部分逆转SGC7901/ADR细胞对ADM耐药性,其机制可能与抑制P-gp功能及下调GST-π表达有关。
【Abstract】 Objective:To explore the reversal effect of arsenic trioxide (As2O3) on the multidrug resistance of human gastric carcinoma SGC7901/ADR cell line to adriamycin(ADM)and its reversal mechanisms.Methods:The non-cytotoxic concentrations of As2O3 and the sensitivity to ADM in SGC7901/ADR cell line were detected by MTT assay.The drug concentration and P-gp function in SGC7901/ADR cell line were measured with flow cytometry(FCM),and the impact of As2O3 on the expressions of GST-πand TOPOⅡin SGC7901/ADR cells was assessed by immunohistochemicai methods.Results:As2O3 at 0.4μmol/L to 0.8μmol/L concentrations was not significantly cytotoxic to SGC7901/ADR cell line.As2O3 could improve the sensitivity of SGC7901/ADR cell line to ADM via inhihiting P-gp function,down-regulating GST-πexpression and increasing the intracellular accumulation of ADM in SGC7901/ADR cell line at 0.8μmol/L concentration.Conclusions:As2O3 is able to partly reverse the re- sistance of SGC7901/ADR cell line to ADM,which may be related to inhibiting the P-gp function and down-regulating of GST-πexpression.
【Key words】 Stomach neoplasms; Drug resistance; multiple; Arsenic; Arsenic trioxide; Tumor cells; cultured;
- 【文献出处】 肿瘤 ,Tumor , 编辑部邮箱 ,2006年11期
- 【分类号】R735.2
- 【被引频次】13
- 【下载频次】108