黄芪水提物抑制PI3K/Akt通路预防肺癌发生的作用及机制研究

目的探讨黄芪水提物对肺癌的抑制作用及相关机制。方法采用MTT实验、Ed U实验以及划痕实验检测黄芪水提物对肺癌A549和H1299细胞的活性、增殖能力和迁移能力的影响,采用流式细胞仪考察黄芪水提物对肺癌细胞周期的影响,通过Western blotting实验检测PI3K/Akt通路相关蛋白表达,通过苯并芘诱导的小鼠肺癌模型观察黄芪水提物对体内肺癌的影响。结果 MTT实验结果表明,黄芪水提物作用于A549和H1299细胞48 h后,细胞的生长活性被抑制;Ed U实验结果表明,黄芪水提物能够显著抑制A549和H1299细胞的增殖能力;对细胞周期考察的实验结果表明,黄芪水提物能够将A549和H1299细胞周期阻滞在S期;划痕实验结果表明,黄芪水提物作用于A549和H1299细胞24 h和48 h后,能够显著抑制细胞的迁移能力;Western blotting实验结果表明,黄芪水提物能够下调A549和H1299细胞磷脂酰肌醇3激酶(PI3K)、磷酸化的磷酸肌醇依赖性蛋白激酶1(p-PDK1)和磷酸化的蛋白激酶B(p-Akt)蛋白表达水平;体内实验结果表明,黄芪水提物能够显著抑制小鼠肺部肿瘤数量及大小。结论黄芪水提物能够抑制肺癌,该机制可能与PI3K/Akt信号通路受阻有关。

Water extracts of Astragali Radix prevent lung carcinogenesis via inhibiting PI3K/Akt pathway

Objective To investigate the inhibitory effect and mechanism of the water extracts of Astragali Radix on lung cancer. Methods The effects of Astragali Radix water extracts on cell viability, cell proliferation and cell migration of A549 and H1299 cells were detected by MTT assay, EdU assay and wound healing assay, respectively. The effect of Astragali Radix water extracts on cell cycle was detected by flow cytometry. Western blotting assay was used to study the expression of related proteins in PI3K/Akt pathway. Finally, the effect of Astragali Radix water extracts on lung cancer in vivo was observed by benzopyrene-induced lung cancer model. Results From the result of MTT assay, the activity of A549 and H1299 cells was inhibited after treated with Astragali Radix water extracts after 48 h. In the EdU experiment, the proliferation ability of A549 and H1299 cells was significantly inhibited by Astragali Radix water extracts in a concentration dependent manner. The study of propidium iodide staining assay result showed that the cell cycle of A549 and H1299 cells was arrested in S phase. In addition, the study of wound healing assay revealed that the migration ability of A549 and H1299 cells was significantly suppressed after 24 h and 48 h treatment by Astragali Radix water extracts. And Western blotting assay revealed that, in drug treatment group, the protein expressions of PI3K, p-PDK1, and p-Akt were down-regulated. Finally, in vivo experiment showed that Astragali Radix water extracts significantly inhibited the number and size of lung tumor nodules in mice. Conclusion It is concluded that Astragali Radix water extracts can inhibit lung cancer. And the mechanism may be related to the inhibition of PI3K/Akt signaling pathway.