缬沙坦通过Akt信号通路抑制宫颈癌Hela细胞增殖、迁移及侵袭的研究

Valsartan Inhibits Proliferation, Migration and Invasion of Cervical Cancer Hela Cells through Akt Signaling Pathway

摘要: 目的：观察血管紧张素II 1型受体拮抗剂缬沙坦(Valsartan)对宫颈癌Hela细胞的增殖、迁移及侵袭的影响及机制。方法：体外培养宫颈癌Hela细胞。采用不同浓度(0.1、1、10和100 μmol/L)的缬沙坦分别处理Hela细胞0、24、48 h，CCK-8法检测Hela细胞的增殖能力。缬沙坦(100 μmol/L)处理Hela细胞24 h后，采用划痕愈合实验和Transwell小室侵袭实验分别检测迁移及侵袭能力，蛋白质印迹法检测缬沙坦(10和100 μmol/L)处理Hela细胞24 h后，Hela细胞中Akt、p-Akt蛋白的表达情况。随后，在Hela细胞中加入Akt激动剂预处理1 h后，再加入缬沙坦(100 μmol/L)培养Hela细胞，采用cck-8法检测Hela细胞增殖能力，采用划痕愈合实验和Transwell小室侵袭实验，检测Hela细胞的迁移和侵袭能力。结果：使用缬沙坦(10和100 μmol/L)处理Hela细胞，能够抑制Hela细胞的增殖作用(p < 0.01)，缬沙坦(100 μmol/L)处理细胞后能够明显抑制Hela细胞的迁移及侵袭能力(p < 0.01)；缬沙坦(100 μmol/L)处理过的Hela细胞中p-Akt蛋白的表达量降低(p < 0.01)。Akt激动剂减弱了缬沙坦对Hela细胞的增殖、迁移及侵袭的抑制作用。结论：缬沙坦对宫颈癌Hela细胞的增殖、迁移及侵袭能力有明显的抑制作用，这种抑制作用可能是通过抑制Akt信号通路实现的。

Abstract: Objective: To observe the effect and mechanism of angiotensin II type 1 receptor antagonist Valsartan on the proliferation, migration and invasion of cervical cancer Hela cells. Methods: Hela cells were cultured in vitro. Different concentrations (0.1, 1, 10, and 100 μmol/L) of valsartan were used to treat Hela cells for 0, 24, and 48 hours, respectively. The proliferation ability of Hela cells was detected by CCK-8 method. After treatment of Hela cells with valsartan (100 μmol/L) for 24 h, the migration and invasion ability were detected by scratch healing test and transwell cell invasion test respectively. Western blotting was used to detect the expression of Akt and p-Akt proteins in HeLa cells after 24 h treatment with Valsartan (10 and 100 μmol/L) Then, HeLa cells were pretreated with Akt agonist for 1 h, and then cultured with Valsartan (100 μmol/L). The proliferation ability of HeLa cells was detected by CCK-8 assay. The migration and invasion ability of HeLa cells were detected by wound-healing assay and Transwell assay. Results: Treatment of Hela cells with 10 and 100 μmol/L valsartan can inhibit the proliferation of Hela cells (p < 0.01). After treatment with valsartan (100 μmol/L), cells can significantly inhibit the migration and invasion ability of Hela cells (p < 0.01); the expression of p-Akt protein in Hela cells treated with 100 μmol/L valsartan was reduced (p < 0.01). Akt agonist eliminates the inhibitory effect of valsartan on the proliferation, migration and invasion of Hela cells. Conclusion: Valsartan has a significant inhibitory effect on the proliferation, migration and invasion of cervical cancer Hela cells. This inhibitory effect may be achieved by inhibiting the Akt signaling pathway.