Abstract: 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.

Key words: Pigment epithelium-derived factor, Nerve growth factors, PI3K/Akt pathway, Phosphatidylinositol 3-kinases, Protein kinases, HeLa cells, Proto-oncogene proteins c-Met