雷帕霉素减缓转基因小鼠肝细胞癌进展

Rapamycin alleviates hepatocellular carcinoma progressing in transgenic mice

目的探究雷帕霉素(rapamycin)对H-ras 12V转基因小鼠肝细胞癌(HCC)进展的影响。方法miRNA高通量测序检测转基因小鼠肝癌及癌旁组织中miRNA表达水平,采用雷帕霉素对转基因小鼠进行治疗干预,形态学检测小鼠肿瘤的变化,RT-qPCR检测miR-183 mRNA表达水平,Western blot检测mTOR、ERK蛋白及miR-183靶基因PDCD4蛋白表达水平。结果肝癌组织中miR-183表达水平较癌旁组织显著升高(P<0.01),PDCD4蛋白水平较癌旁组织显著降低(P<0.05)。雷帕霉素干预后,与对照组相比,雷帕霉素组肝肿瘤整体总数显著下降(P<0.05),肝系数显著降低(P<0.05),ERK磷酸化水平显著升高(P<0.05),miR-183表达水平显著下降(P<0.05),其靶基因PDCD4表达水平显著升高(P<0.05)。结论雷帕霉素可减缓H-ras 12V转基因小鼠肝癌的进展。

Objective Exploring the influence of rapamycin on the progressing of hepatocellular carcinoma(HCC)in H-ras 12V transgenic mice.Methods The expression level of miRNA in liver tissue and peritumor tissue of transgenic mice was detected by high-throughput sequencing of miRNAs.Treatment of transgenic mice with rapamycin and the changes of tumor morphology were detected.The miR-183 expression levels were detected by RT-qPCR.The protein expression levels of mTOR,ERK and PDCD4,the downstream target gene of miR-183,were detected by Western blot.Results Compared with the peritumor tissue,the miR-183 expression in hepatocellular carcinoma tissue was increased significantly(P<0.01).The protein expression levels of PDCD4 were decreased significantly(P<0.05).Compared with the control group,after intervention with rapamycin,the counting of liver tumors decreased significantly(P<0.05).The liver co-efficient decreased significantly(P<0.05).The ERK phosphorylation increased significantly(P<0.05).The miR-183 expression was decreased significantly(P<0.05).The protein level of PDCD4 increased significantly(P<0.05).Conclusions Rapamycin can alleviate hepatocellular carcinoma progression in H-ras 12V transgenic mice.