安德罗格拉福利德向EGFR,以阻碍人类乳腺癌细胞中的上皮层-介质酶过渡
Chutima Kaewpiboon1, Nawong Boonnak2, Abdul-Wahab Salae3
1Department of Biology, Faculty of Science and Digital Innovation, Thaksin University, Phatthalung 93210, Thailand.
Journal of pharmaceutical and biomedical analysis
|June 18, 2024
概括
安德罗格拉福利德 (ADGL) 通过向EGFR来抑制乳腺癌转移,减少表皮-介质细胞过渡 (EMT). 这种天然剂在减少侵袭性和使癌细胞对亡敏感方面显示出前途.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 自然产品 化学 化学
背景情况:
- 尽管进行了初级手术治疗,乳腺癌的转移和侵袭性仍然是重大挑战.
- 化疗疗效果有限,需要寻找具有较少副作用的新型天然治疗剂.
- 安德罗格拉福利德 (ADGL) 是一种来自Andrographis paniculata的化合物,具有抗癌特性,但其作用机制,特别是与转移有关的作用机制,尚未完全理解.
研究的目的:
- 为了研究Andrographolide (ADGL) 在乳腺癌中的抗转移作用背后的分子机制.
- 为了确定表皮-介质细胞转换 (EMT) 和相关蛋白质 (EGFR,STAT1,HDAC4) 在乳腺癌转移中的作用.
- 通过评估ADGL对EMT,细胞迁移,入侵和细胞亡的影响来评估ADGL作为治疗剂的潜力.
主要方法:
- 在非转移性 (MCF7) 与高度转移性 (MDA-MB-231) 乳腺癌细胞中对EMT相关蛋白质表达 (E-cadherin,N-cadherin,vimentin) 的比较分析.
- 在MDA-MB-231细胞中使用小干扰RNA (siRNAs) 抑制关键蛋白质 (EGFR,STAT1,HDAC4),以评估它们在EMT中的作用.
- 用ADGL对MDA-MB-231细胞进行治疗,以评估其对细胞迁移,入侵,蛋白质表达和细胞亡的影响,包括用siRNAs进行组合治疗.
主要成果:
- 与MCF7细胞相比,高度转移的MDA-MB-231细胞表现出较高的N-cadherin,vimentin,EGFR,STAT1和HDAC4水平,以及较低的E-cadherin,这证实了它们与EMT的关联.
- 抑制EGFR,STAT1或HDAC4减少了MDA-MB-231细胞中的EMT,突出了它们在转移中的关键作用.
- 治疗ADGL抑制了MDA-MB-231细胞迁移和入侵,恢复了E-cadherin,降低了N-cadherin和vimentin,并以剂量依赖的方式调节了EGFR,STAT1和HDAC4表达/活性. 结合ADGL和siRNA治疗显著增强了亡.
结论:
- EGFR,STAT1和HDAC4是人类乳腺癌细胞上皮层-介质细胞过渡 (EMT) 和转移的关键调节者.
- 安德罗格拉福利德 (ADGL) 通过向EGFR并因此抑制EMT,有效地抑制乳腺癌细胞迁移和入侵.
- ADGL显示出作为乳腺癌治疗剂的潜力,特别是在减少转移方面,其有效性可以通过组合疗法来提高.
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