原蛋白和PKM2之间的相互作用抑制了结直肠癌的进展
Jiangying Shi1, Xiaodan Ji1, Shuhua Shan1
1Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.
The Journal of nutritional biochemistry
|August 19, 2023
概括
作为一种天然化合物,apigenin通过向酸激酶M2 (PKM2) 来抑制结肠直肠癌. 它限制了癌细胞的糖解和生长,显示出作为安全治疗剂的承诺.
科学领域:
- 生物化学 生物化学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 在水果和蔬菜中发现的黄胺 (apigenin) 具有潜在的抗癌特性,具有低毒性.
- 针对apigenin抗癌作用的特定分子标和机制在很大程度上仍未被阐明.
- 了解apigenin的直接目标对于开发它作为治疗瘤的治疗剂至关重要,特别是结肠直肠癌 (CRC).
研究的目的:
- 在结直肠癌中识别apigenin的直接分子标.
- 为了确定特定的氨基酸部位参与apigenin与其目标的相互作用.
- 阐明阿皮基因因行使其抗CRC作用的机制.
主要方法:
- 在LS-174T细胞中,与PKM2 Knockdown进行的apigenin抗CRC活性和pyruvate kinase M2 (PKM2) 表达之间的相关性分析.
- 拉向测定和MALDI-TOF/TOF分析以确定HCT-8细胞中阿皮基宁和PKM2之间的直接相互作用.
- 位点定向突变发生和功能测试,以确认氨酸残留433 (K433) 在PKM2与阿皮原蛋白结合中的作用.
主要成果:
- 原蛋白的抗CRC活性与PKM2表达呈正相关性,PKM2的淘汰降低了原蛋白的疗效.
- 在HCT-8细胞中证实了apigenin与PKM2的直接结合.
- 氨酸残留物433 (K433) 被确定为原蛋白与PKM2.2结合的关键氨基酸位点.
- 原蛋白通过向K433位点的PKM2来抑制CRC细胞中的糖解,导致细胞增殖减少和细胞亡增加.
- 在体内,apigenin治疗显著减弱了瘤的生长,没有可观察到的不良影响.
结论:
- 原蛋白直接针对K433残留物中的PKM2抑制结直肠癌.
- 原蛋白限制癌细胞糖解,为CRC提供了一种新的治疗策略.
- 原蛋白显示出显著的抗瘤疗效,具有良好的安全性,将其定位为CRC预防和治疗的有前途的PKM2抑制剂.
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