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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

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【作者】 杨鸿武杨贤东关宏伟

【Author】 YANG Hong-wu~1 YANG Xian-dong~2 GUAN Hong-wei~1 1.The Pathology Department of First Affiliated Hospital,Dalian Medical University,Dalian 116011,China; 2.The Stomatology College,Dalian Medical University,Dalian 116027,China

【机构】 大连医科大学附属第一医院病理科大连医科大学口腔医学院大连医科大学附属第一医院病理科 大连116011大连116027大连116011

【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.

  • 【分类号】R735.2
  • 【被引频次】13
  • 【下载频次】108
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