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

作　　者：杨鸿武[1] 杨贤东[2] 关宏伟[1] 

机构地区：[1]大连医科大学附属第一医院病理科,大连116011 [2]大连医科大学口腔医学院,大连116027

出　　处：《肿瘤》2006年第11期994-996,共3页Tumor

摘　　要：目的：探讨三氧化二砷(As_2O_3)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As_2O_3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 As_2O_3对耐药细胞SGC7901/ ADR无明显毒性,0．8μmol/L的As_2O_3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：As_2O_3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。Objective：To explore the reversal effect of arsenic trioxide （As2 O3 ） 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-π and TOPOⅡ in SGC7901/ADR cells was assessed by immunohistochemical methods. Results： As2O3 at 0.4 μmol/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 inhibiting P-gp function,down-regulating GST-π expression 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 resistance of SGC7901/ADR cell line to ADM,which may be related to inhibiting the P-gp function and down-regulating of GST-π expression.

关 键 词：胃肿瘤 抗药性 多药 砷 三氧化二砷 肿瘤细胞 培养的 

分 类 号：R735.2[医药卫生—肿瘤] R73-361[医药卫生—临床医学]