miRNA-34a在胃癌细胞KATOⅢ中对5-Fu的增敏作用

miRNA-34a regulate sensitivity to 5-Fu in gastric cancer cells

目的研究miR-34a在胃癌细胞KATOⅢ中对5-氟尿嘧啶(5-Fu)化疗敏感性的影响。方法采用定量PCR检测人正常胃黏膜细胞GES-1、胃癌细胞株BGC823、KATOⅢ、MGC803、MKN 45及SGC7901,检测5例胃癌及癌旁正常组织中miRNA-34a的表达水平。选择恶性程度较高的KATOⅢ细胞进一步研究,通过miR-34amimics上调胃癌细胞KATOⅢ中miR-34a的表达,通过MTT法检测肿瘤细胞对不同浓度5-Fu耐药活性的变化,以及肿瘤细胞增殖能力的变化。结果胃癌细胞BGC823,KATOⅢ,MGC803,MKN 45及SGC7901中miRNA-34a处于相对低表达水平,miR-34a在5例胃癌组织中的表达低于癌旁正常组织。选取miR-34a低表达的KATOⅢ细胞株,通过miR-34amimics上调miR-34a的表达后,药物浓度反应曲线显示,与negative control(NC)组比较,miR-34amimics组IC_(50)值下降(P<0.05),肿瘤细胞的增殖能力被miR-34a抑制(P<0.05)。结论 miR-34a在胃癌细胞KATOⅢ中提高了5-Fu的药物敏感性,同时抑制胃癌细胞KATOⅢ的增殖能力。

Objective To explore the function of miRNA-34a on chemosensitivity of 5-Fu in gastric cancer cell KATOⅢ. Methods The expression of miRNA-34a in gastric cancer cell lines BGC823,KATOⅢ,MGC803,MKN 45 and SGC7901were examined by real-time PCR.Also 5 gastric cancer tissues and adjacent normal tissues were selected from gastric cancer specimens and the expression of miR-34a was examined by real-time PCR.The alteration of KATOⅢ cells resistance （IC 50 ）to 5-Fu was detected by MTT after miR-34a was up-regulated by miRNA mimics.Also the MTT was used to detect KATOⅢ cell proliferation after miR-34a up-regulated by miRNA mimics. Results The miRNA-34a was in low expression statue in BGC823,BGC823,KATOⅢ,MGC803,MKN 45 and SGC7901cell lines （ P〈 0.05）.Compared with the adjacent normal tissue,miR-34a was relatively low expressed in gastric cancer tissue （ P〈 0.05）.Compared with negative control,the IC 50 of 5-Fu decreased in miR-34a mimics group in KATOⅢ cells,and cell proliferation was reduced in miR-34a mimics group （ P〈 0.05）. Conclusion Our findings suggested that miR-34a inhibit gastric cancer cell KATOⅢ and induce chemo-sensitization in P53-deficient cell lines.