色素上皮衍生因子通过抑制PI3K/Akt通路降低宫颈癌HeLa细胞活性和侵袭相关蛋白表达

目的：探讨色素上皮衍生因子（PEDF）通过抑制磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）信号通路，从而下调人宫颈癌HeLa细胞的活性和侵袭相关蛋白c-Met表达的相关机制。方法：选取本院病理已确诊的40例宫颈癌样本及对应的40例癌旁正常组织样本，通过免疫组织化学法检测PEDF、PI3K和p-Akt蛋白的表达。在细胞水平分为正常宫颈上皮细胞HCerEpiC组、HeLa组、HeLa+PEDF组、HeLa+PEDF+PI3K/Akt激活剂组和HeLa+PI3K/Akt抑制剂组。通过蛋白质印迹（Western blotting）检测各组细胞内PEDF、PI3K、p-Akt、Akt及c-Met蛋白的表达水平，CCK-8法检测各组细胞的活性。结果：宫颈癌样本和HeLa细胞中的PI3K/Akt通路显著激活，且PEDF表达显著下降（P＜0.01）。PEDF可以显著抑制HeLa细胞中PI3K/Akt激活和细胞活性以及侵袭相关蛋白水平的增加（P＜0.01）。Akt激活剂可以逆转PEDF对HeLa细胞活性和侵袭蛋白表达的影响，而激活PI3K无法改变PEDF的作用。单纯的药物抑制PI3K/Akt通路不足以模拟PEDF对HeLa细胞的作用。结论：PEDF通过PI3K/Akt双重抑制作用降低HeLa细胞活性和侵袭相关蛋白表达，这为临床上PEDF治疗宫颈癌提供了新的思路和理论依据。

Pigment Epithelium-Derived Factor Reduces HeLa Cell Viability and Invasion-Related Protein Expression by Inhibiting PI3K/Akt Pathway

Objective: To investigate the roles and mechanisms of pigment epithelial-derived factor (PEDF) in down-regulating the viability and invasion-related c-Met protein expression of HeLa cells via inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Methods: 40 cases of cervical cancer diagnosed in our hospital and 40 corresponding normal uterus samples were selected. The expression of PEDF, PI3K and p-Akt were detected by immunohistochemistry. At the cellular level, it was divided into normal cervical epithelial HCerEpiC group, HeLa group, HeLa+PEDF group, HeLa+PEDF+PI3K/Akt activator group and HeLa+PI3K/Akt inhibitor group. The expression levels of PEDF, PI3K, p-Akt, Akt and c-Met protein in each group were detected by Western blotting. The cell viability of each group was detected by CCK-8 assay. Results: The PI3K/Akt pathway was significantly activated in cervical cancer samples and HeLa cells, and the expression of PEDF was significantly decreased (P＜0.01). PEDF significantly inhibited PI3K/Akt activation, cell viability and invasion-related protein level of HeLa cells (P＜0.01). Akt activator can reverse the effects of PEDF on HeLa cell viability and invasion protein expression, while activation of PI3K can not affect the effects of PEDF. The simple drug inhibition of the PI3K/Akt pathway is insufficient to mimic the effects of PEDF on HeLa cells. Conclusions: PEDF reduces HeLa cell viability and invasion-related protein expression through the dual inhibitory effect of PI3K/Akt, which provides a novel theoretical basis for the clinical treatment of cervical cancer with PEDF.