粉防己碱对人胃癌耐药细胞锌指蛋白139、多药耐药基因表达的影响

目的探讨粉防己碱（tetrandrine，TET）对胃癌细胞及耐药细胞中锌指蛋白139（zincfingerprotein139，ZNFl39）及多药耐药（multidrugresistance，MDR）基因的影响。方法MTT法检测不同浓度（0．5、1．0、1．5、2．0、2．5闪，mL）TET对胃癌细胞SGC7901、SGC7901／ADR细胞株的抑制作用；通过RT-PCR法检测TET作用前后SGC7901／ADR细胞内ZNFl39、MRP-1、MDR1、GST-π表达情况，以Spearman相关分析检验ZNF139与各多药耐药因子之间关系并计算相关系数。结果MTT结果显示，2．0μg／mL及以下浓度TET对SGC7901、SGC7901／ADR两种细胞的抑制率均〈10％；在SGC7901／ADR细胞中ZNF139、MRP-1、MDRl、GST-πmRNA表达高于SGC7901细胞（均P〈0．05）；TET能抑制SGC7901／ADR细胞中ZNF139、MRP-1、MDR1、GST-πmRNA的水平（均P〈0．05）；TET作用前SGC7901／ADR细胞中ZNF139与MRP．1、MDR1存在相关关系，作用后这种相关性仍存在（均P〈0．05）。结论TET可能通过抑制ZNF139下调、MDR1、MRP1的表达从而逆转胃癌耐药细胞MDR表型。

Effect and Mechanisms of TET on Human Gastric Carcinoma Cell Line SGC7901 and SGC7901/ ADR

Objective To investigate the effect of tetrandrine （TET） on zinc finger protein 139 （ZNF139） and multidrug resistance （MDR） of human gastric carcinoma cell lines and possible mecha- nisms. Methods Cultured SGC7901 and SGC7901/ADR were treated with TET （0.5, 1.0, 1.5, 2.0, and 2.5 μg/mL）, then inhibition rates were measured by M-IF assay in vitro. The expressions of ZNF139, MRP-1, MDR1, and GST-π were detected by RT-PCR. The correlation between ZNF139 and each multi- drug resistance factor was analyzed using Spearman correlation analysis, and the coefficient correlation was calculated. Results The inhibition rate of TET （ ≤2.0 μg/mL） for SGC7901 and SGC7901/ADR was less than 10% with MI-I-assay. Expressions of ZNF139, MRP-1, MDR1, and GST-μ mRNA were higher in SGC7901/ADR than in SGC7901 （all P 〈0.05）. The expressions of ZNF139, MRP-1, MDR1, and GST-πwere down-regulated in SGC7901/ADR cells efficiently （all P 〈0.01 ）. Positive correlation existed between ZNF139 and MRP-1, ZNF139 and MDR1 before treated by TET in SGC7901/ADR, and this relationship also existed in SGC7901/ADR cells after treated by TET （all P 〈0.05）. Conclusion TET could achieve MDR reversion in gastric cancer cells by down-regulating the expression of ZNF139, MRP-1, and MDRI.