乙型肝炎病毒感染的核类型差异性调节肝细胞中生长因子信号传递
Ryogo Shimizu1, Kazuhisa Murai1, Kensuke Tanaka1
1Department of Clinical Laboratory Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Hepatology communications
|January 5, 2024
概括
核酸相似物 (NtAs),但不是核酸相似物 (NsAs),直接抑制肝瘤细胞生长,并可能通过影响胰岛素受体信号来降低慢性乙型肝炎患者肝细胞癌 (HCC) 风险.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 临床研究表明,与恩特卡维尔相比,诺福维尔二氧化烟酸可能会降低慢性乙型肝炎患者的肝细胞癌 (HCC) 风险.
- 这两种药物之间在生物化学或病毒学缓解方面没有显著差异.
研究的目的:
- 研究核酸相似物 (NSAs) 和核酸相似物 (NtAs) 对肝瘤细胞生长的体外和体内影响.
- 评估NSA和NTA对生长信号分子和胰岛素受体 (INSR) 结合的影响.
主要方法:
- 在肝瘤细胞系和PXB细胞的体外研究中,使用了NSA (拉米武丁,恩特卡维尔) 和NTA (阿德福维尔迪索普罗克西尔,特诺福维尔迪索普罗克西尔烟酸盐,特诺福维尔阿拉芬胺).
- 使用老鼠异种移植模型进行体内评估.
- 通过热转移测定分析蛋白质酸化概况和胰岛素受体 (INSR) 结合.
主要成果:
- 在体外和体内,NtAs在肝瘤细胞上表现出直接的增长抑制作用,与NSA不同.
- NtAs显著降低了酸化胰岛素受体 (p-INSRβ) 和下游信号分子 (p-IRS1,p-AKT,p-Gab1,p-SHP2),以及p-表皮生长因子受体和p-AKT.
- 这些效应在慢性乙型肝炎患者的PXB细胞和非瘤肝组织中观察到,并归因于前药物NTA,而不是其代谢物.
结论:
- 核酸类似物 (NtAs) 与生长因子受体的ATP结合部位结合,抑制自酸化.
- 这种机制可能解释了慢性乙型肝炎患者接受NTA治疗时观察到的HCC风险降低.
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