雷帕霉素减缓转基因小鼠肝细胞癌进展

doi:10.16352/j.issn.1001-6325.2023.08.1241

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (8): 1241-1246.doi: 10.16352/j.issn.1001-6325.2023.08.1241

雷帕霉素减缓转基因小鼠肝细胞癌进展

林映雪¹, 崔海鹏^2*, 王爱国^3*, 姚银辉¹, 赵娟²

1.承德医学院附属医院药学部,河北承德 067000;
2.承德医学院病理生理学教研室,河北承德 067000;
3.大连医科大学实验动物中心,辽宁大连 116044

收稿日期:2023-02-06 修回日期:2023-05-30 出版日期:2023-08-05 发布日期:2023-07-26
通讯作者: ^*han984746810@163.com;wangaiguotl@hotmail.com
基金资助:
河北省自然科学基金(H2020406011);河北省医学科学研究课题计划(20200183);河北省高等学校科学研究青年基金(QN2023017)

Rapamycin alleviates hepatocellular carcinoma progressing in transgenic mice

LIN Yingxue¹, CUI Haipeng^2*, WANG Aiguo^3*, YAO Yinhui¹, ZHAO Juan²

1. Department of Pharmacy, Affiliated Hospital of Chengde Medical University, Chengde 067000;
2. Department of pathophysiology, Chengde Medical University, Chengde 067000;
3. Laboratory Animal Center, Dalian Medical University, Dalian 116044, China

Received:2023-02-06 Revised:2023-05-30 Online:2023-08-05 Published:2023-07-26
Contact: ^*han984746810@163.com;wangaiguotl@hotmail.com

摘要/Abstract

摘要： 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。

关键词: 肝细胞癌, 雷帕霉素, miR-183, 程序性细胞死亡因子4

Abstract: 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.

Key words: hepatocellular carcinoma, rapamycin, miR-183, PDCD4

中图分类号:

R735.7

林映雪, 崔海鹏, 王爱国, 姚银辉, 赵娟. 雷帕霉素减缓转基因小鼠肝细胞癌进展[J]. 基础医学与临床, 2023, 43(8): 1241-1246.

LIN Yingxue, CUI Haipeng, WANG Aiguo, YAO Yinhui, ZHAO Juan. Rapamycin alleviates hepatocellular carcinoma progressing in transgenic mice[J]. Basic & Clinical Medicine, 2023, 43(8): 1241-1246.

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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

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