Role of IL-6/STAT3 signaling pathway in high-risk human papillomavirus associated cervical cancer cells / 中国医师杂志

ABSTRACT

Objective:To investigate the role and mechanism of interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway in proliferation, invasion and apoptosis of cervical cancer cells infected by high-risk human papillomavirus (HPV).Methods:HPV-18 positive HeLa cells cultured in vitro were divided into control group (normal cultured), IL-6 group (stimulated with 50 ng/ml IL-6 for 24 h) and IL-6 + AG490 group (stimulated with 50 ng/ml IL-6 and 100 μmol/L STAT3 signaling pathway inhibitor AG490 for 24 h). Methyl thiazolyl tetrazolium (MTT) assay was used to detect the cell survival rate. The ability of cell clone formation was detected by plate clone formation assay. The cell invasion was detected by transwell chamber assay. The cell apoptosis was detected by flow cytometry. Western blot was used to detect the protein expression levels of STAT3, phosphorylation of (p)-STAT3, B-cell lymphoma-2 gene (Bcl-2), CyclinD1 and matrix metalloproteinase-9 (MMP-9). Results:Compared with those in the control group, the cell survival rate, clone formation rate, number of invasive cells and the protein expression levels of p-STAT3, Bcl-2, CyclinD1 and MMP-9 in IL-6 group were significantly higher, while the apoptosis rate was significantly lower ( P<0.05); at the same time, compared with those in IL-6 group, the cell survival rate, clone formation rate, the number of invasive cells and the protein expression levels of p-STAT3, Bcl-2, CyclinD1 and MMP-9 in IL-6 + AG490 group were significantly lower, while the apoptosis rate was significantly higher ( P<0.05). Conclusions:IL-6/STAT3 signaling pathway plays an important role in the malignant progression of high-risk HPV infected cervical cancer cells, and its mechanism may be related to the up-regulation of CyclinD1, MMP-9, Bcl-2 protein expressions.