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Runx3基因对HepG2细胞顺铂耐药性的影响

, PP. 813-816

Keywords: Runx,耐药,肝癌,DNA甲基化,细胞周期,RNA干扰

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Abstract:

目的探讨Runx3基因对HepG2细胞耐药性的影响及可能机制。方法取在1.6μg/ml顺铂(CDDP)下生长良好的HepG2耐药细胞(HepG2/CDDP-1.6),建立耐药HepG2/CDDP的动态变化模型HepG2/CDDP/2.0,并予以甲基转移酶抑制剂5-氮-2′-脱氧胞苷(5-Aza-CdR)处理;将Runx3-shRNA表达载体转染HepG2/CDDP-1.6细胞,RT-PCR检测处理及转染前后细胞Runx3mRNA的表达。MTT法检测细胞的增殖活性,流式细胞仪分析细胞周期,Hoechst33258检测凋亡,Westernblot检测P-gp表达的变化。结果在动态变化模型中随CDDP诱导时间的延长,Runx3mRNA的表达逐渐降低。5-Aza-CdR处理后Runx3mRNA的表达增加,细胞生长受到明显抑制,S期细胞逐渐增加,凋亡细胞明显增多,细胞内P-gp的表达减少。转染Runx3-shRNA载体后HepG2/CDDP-1.6细胞对CDDP的耐受性增强,G1期细胞增加,P-gp的表达增加。结论Runx3基因的表达可抑制HepG2/CDDP耐药的形成,提高HepG2/CDDP细胞对化疗药物的敏感性。

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