通过通过AMPK/mTOR减弱糖解质通路,探索阿斯塔加林在三阴性乳腺癌细胞中的抗癌潜力
Ahmad Zeb1,2, Walizeb Khan1, Waseem Ul Islam3,4
1Department of Biosciences, COMSATS University 45550, Islamabad, Pakistan.
Current medicinal chemistry
|July 29, 2024
概括
阿斯塔加林 (ASG) 通过向有氧糖解来抑制乳腺癌细胞的增殖. ASG通过AMPK/mTOR途径调节关键的糖解酶和葡萄糖吸收.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 有氧糖解对于癌细胞的存活和进展至关重要.
- 向糖解路径为癌症治疗提供了一种治疗策略.
研究的目的:
- 为了研究阿斯特拉加林 (ASG) 对乳腺癌细胞的抗癌作用.
- 阐明ASG通过AMPK/mTOR信号级联对糖解路径的作用机制.
主要方法:
- 从Haplophyllum tuberculatum中分离出的ASG用于治疗MDA-MB-231乳腺癌细胞.
- 测试包括MTT用于增殖,色度测试用于葡萄糖吸收和乳酸盐,qRT-PCR用于糖解酶 (HK-2,LDH-A,GLUT-1) 的mRNA表达,以及西部斑块蛋白质水平.
- 对于ASG与AMPK和mTOR蛋白质进行了in silico分子对接.
主要成果:
- ASG证明了对MDA-MB-231细胞的剂量和时间依赖的抗增殖作用.
- ASG显著降低了GLUT-1,LDH-A和HK-2的mRNA和蛋白质表达,减少了葡萄糖的摄取和乳酸盐的产生.
- ASG激活了AMPK和抑制了mTOR,这些效应被AMPK抑制剂 (化合物C) 逆转. 分子对接表示ASG与AMPK和mTOR结合.
结论:
- 阿斯特拉加林抑制MDA-MB-231乳腺癌细胞中的有氧糖解和增殖.
- 该机制涉及AMPK/mTOR通路的调节.
- ASG显示出作为向糖解的抗癌剂的潜力.
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