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以罗格列酮和阿霉素为重点的联合治疗策略用于胰岛素抵抗性肝癌

Combination treatment strategies with a focus on rosiglitazone and adriamycin for insulin resistant liver cancer.

作者信息

Dang Yi-Fan, Yang Shao-Hui, Jiang Xiao-Ning, Gong Fu-Lian, Yang Xiao-Xia, Cheng Yan-Na, Guo Xiu-Li

机构信息

Department of Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, PR China.

Shandong Wendeng Osteopathic Hospital, Wendeng, PR China.

出版信息

J Drug Target. 2021 Mar;29(3):336-348. doi: 10.1080/1061186X.2020.1844216. Epub 2021 Jan 18.

Abstract

Insulin resistance promotes the occurrence of liver cancer and decreases its chemosensitivity. Rosiglitazone (ROSI), a thiazolidinedione insulin sensitiser, could be used for diabetes with insulin resistance and has been reported to show anticancer effects on human malignant cells. In this paper, we investigated the combination of ROSI and chemotherapeutics on the growth and metastasis of insulin-resistant hepatoma. assay, ROSI significantly enhanced the inhibitory effects of adriamycin (ADR) on the proliferation, autophagy and migration of insulin-resistant hepatoma HepG2/IR cells downregulation of EGFR/ERK and AKT/mTOR signalling pathway. In addition, ROSI promoted the apoptosis of HepG2/IR cells induced by ADR. assay, high fat and glucose diet and streptozotocin (STZ) induced insulin resistance in mice by increasing the body weight, fasting blood glucose (FBG) level, oral glucose tolerance, fasting insulin level and insulin resistance index. Both the growth of mouse liver cancer hepatoma H22 cells and serum FBG level in insulin resistant mice were significantly inhibited by combination of ROSI and ADR. Thus, ROSI and ADR in combination showed a stronger anti-tumour effect in insulin resistant hepatoma cells accompanying with glucose reduction and might represent an effective therapeutic strategy for liver cancer accompanied with insulin resistant diabetes.

摘要

胰岛素抵抗促进肝癌的发生并降低其化疗敏感性。罗格列酮(ROSI)是一种噻唑烷二酮类胰岛素增敏剂,可用于治疗伴有胰岛素抵抗的糖尿病,据报道对人类恶性细胞具有抗癌作用。在本文中,我们研究了ROSI与化疗药物联合使用对胰岛素抵抗性肝癌生长和转移的影响。实验表明,ROSI显著增强了阿霉素(ADR)对胰岛素抵抗性肝癌HepG2/IR细胞增殖、自噬和迁移的抑制作用,并下调了EGFR/ERK和AKT/mTOR信号通路。此外,ROSI促进了ADR诱导的HepG2/IR细胞凋亡。实验表明,高脂高糖饮食和链脲佐菌素(STZ)通过增加体重、空腹血糖(FBG)水平、口服葡萄糖耐量、空腹胰岛素水平和胰岛素抵抗指数诱导小鼠胰岛素抵抗。ROSI与ADR联合使用显著抑制了胰岛素抵抗小鼠肝癌H22细胞的生长和血清FBG水平。因此,ROSI与ADR联合使用在胰岛素抵抗性肝癌细胞中显示出更强的抗肿瘤作用,同时伴有血糖降低,可能是治疗伴有胰岛素抵抗性糖尿病的肝癌的有效治疗策略。

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