益生菌衍生的银纳米颗粒向mTOR/MMP-9/BCL-2/依赖AMPK激活用于肝癌治疗
Alaa Elmetwalli1,2, Mohamed O Abdel-Monem3, Ali H El-Far4
1Department of Clinical Trial Research Unit and Drug Discovery, Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt. dr.prof2011@gmail.com.
Medical oncology (Northwood, London, England)
|April 4, 2024
概括
使用Lactobacillus acidophilus合成的银纳米粒子 (AgNPs) 对肝癌细胞表现出强大的抗癌作用. 这些AgNP通过抑制AMPK/mTOR信号传递,选择性地诱导HepG2细胞的亡,提供了一个有前途的纳米医学策略.
科学领域:
- 纳米技术和癌症治疗方法
- 纳米颗粒的微生物合成
- 分子生物学和瘤学分子生物学和瘤学
背景情况:
- 纳米技术为癌症治疗提供了创新的方法.
- 使用Lactobacillus acidophilus合成的银纳米粒子 (AgNPs) 具有已证明的抗癌特性.
- 以前的研究表明,AgNP可能会抑制AMPK/mTOR信号传递和BCL-2表达,这是癌症进展的关键途径.
研究的目的:
- 为了研究乳杆菌酸性合成的AgNP对HepG2肝癌细胞的疗效.
- 为了评估AgNP对细胞增殖,自和细胞亡的影响,在体外和在体内.
- 阐明AgNP诱导的抗癌作用背后的分子机制.
主要方法:
- 使用RBIM菌株的Lactobacillus acidophilus合成AgNP.
- 使用FTIR和UV可见光谱学对AgNP进行表征.
- 在体外对HepG2和WI-38细胞进行测试,以评估细胞毒性,亡和基因表达 (AMPK,mTOR,BCL-2,MMP-9,α-SMA,TNF-α,IL-33).
- 在基分子对接中预测AgNP与AMPK的相互作用.
主要成果:
- 乳杆菌酸性有效合成了具有证实表面功能组的AgNP.
- 与正常的WI-38细胞 (IC50 = 154.1μg/ml) 相比,AgNP对HepG2细胞具有选择性毒性 (IC50 = 4.217μg/ml).
- AgNPs诱导了亡,上调了促炎细胞因子 (TNF-α,IL-33),增加了谷氨,激活了AMPK,并抑制了mTOR,BCL-2,MMP-9和α-SMA.
- 分子对接建议AgNP通过结合其活性部位来抑制AMPK活性,从而导致mTOR抑制和亡诱导.
结论:
- 来自乳杆菌酸性的AgNP在抑制HepG2细胞增殖和诱导亡方面是有效的.
- 抗癌机制涉及AMPK/mTOR途径的抑制和关键癌症相关基因的调制.
- AgNP代表了肝癌的有希望的纳米治疗策略,可能增强免疫反应.
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