[Effects of Src on cervical cancer cells proliferation and apoptosis through ERK signal transduction pathway]

Abstract

Objective: To explore the effect of Src on cervical cancer cells through ERK signal transduction pathway. Methods: Experimental study was carried out in vitro. Cervical cancer cell lines Hela (HPV-positive) and C33A (HPV-negative) were treated with Src kinase inhibitor PP2. Then, the cell cycle and apoptosis of each group were evaluated by using flow cytometry (FCM). Western blotting and Real-time PCR were used to detect the levels of the expression of ERK 1/2, c-Fos and c-Jun mRNA and protein respectively. The database was established and analyzed with SPSS statistical software (version 20.0). Results: After down-regulating Src, the cell proliferation was inhibited and cell apoptosis was induced. The proportions of G0/G1 stage of Hela and C33A cell in cell cycle increased while G2/M and S stages decreased. Meanwhile, the mRNA levels of ERK 1, ERK 2, c-Fos and c-Jun increased. And the expression levels of ERK 1/2, phosphorylated ERK 1/2 (p-ERK 1/2) and phosphorylated c-Fos (p-c-Fos) protein decreased, while c-Jun and phosphorylated c-Jun (p-c-Jun) protein expression increased. In addtion, the change level of Hela cell, p-ERK 1/2 and c-Fos protein were lower than that of C33A cell before and after the Src inhibition. Conclusions: Src, involved in regulating the expression of key factors of the ERK signal transduction pathway including p-ERK 1/2 and p-c-Fos, might be capable of promoting the proliferation of cervical cancer cells and inhibiting their apoptosis. The infection with HPV might have adjustable effect on this process.

Keywords: Cervical cancer cell; ERK signal transduction; HPV; Src.