通过向mTOR,SGLT2i可以延迟c-Myc诱导的HCC进展
Huiling Rao1, Xiaotong An2, Xinyang Qu2
1School of Basic Medical Sciences, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, People's Republic of China; Department of Medical Engineering, The First Affiliated Hospital of Army Medical University, Chongqing 400000, People's Republic of China.
糖尿病药物empagliflozin (EMPA) 在治疗肝癌方面表现有前途. 它通过向mTOR途径来抑制c-Myc驱动的肝细胞癌 (HCC) 的进展.
科学领域:
- 在瘤学瘤学.
- 代谢疾病 代谢疾病
- 药理学 药理学是指药理学的学科.
背景情况:
- 肝细胞癌 (HCC) 是一种主要的肝癌,由代谢重编程驱动.
- 瘤基因c-Myc通过调节基因转录,在HCC发育中发挥关键作用.
- 恩帕格利弗洛辛 (EMPA) 是一种-葡萄糖共运输体-2 抑制剂 (SGLT2i),用于治疗2型糖尿病,并显示出潜在的抗癌作用.
研究的目的:
- 研究c-Myc,EMPA和mTOR在HCC中的相互作用.
- 评估EMPA作为HCC的潜在治疗剂的疗效.
主要方法:
- 在小鼠中,通过c-Myc等离子体转染诱导HCC.
- 定量PCR和免疫组织化学评估了SGLT2表达.
- 在体内和体外研究中评估了SGLT2抑制剂 (EMPA,canagliflozin).
- 网络药理学,分子对接,CETSA和西部斑点分析探索了EMPA的机制.
主要成果:
- c-Myc过度表达导致HCC组织中SGLT2表达增加.
- SGLT2 抑制剂减少了肝癌的进展和肝脏脂肪的积累.
- 在c-Myc转移的细胞中,EMPA抑制了增殖,并抑制了mTOR激活.
结论:
- EMPA显示出延迟HCC发育和进展的潜力.
- 恩帕的抗癌作用与mTOR通路的抑制有关.
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