The pro-angiogenic factors stimulated by human papillomavirus type 16 E6 and E7 protein in C33A and human fibroblasts.

To investigate the pro-angiogenic factors stimulated by human papillomavirus type 16 E6 and E7 protein in C33A and human fibroblasts. HPV-16 E6 and E7 genes were transfected into C33A and HFB to detect the profiling of angiogenesis-associated factors with the TranSignal angiogenesis antibody array. The mRNA and protein levels of the cytokines were examined by traditional RT-PCR and Western blotting in both cell lines before and after transfection of HPV-16 E6 and E7. HPV-16 E6 and E7 genes were successfully transfected into C33A and HFB cells. On the sheet of antibody array, after transfection of HPV-16 E6 and E7, 6 other cytokines, Ang-1, FGFalpha, HGF, IL-6, IP-10 and PIGF besides VEGF, were detected at higher levels in C33A cells. Expression of 7 other cytokines besides IL-8, Ang-1, IL-1alpha, IL-1beta, HGF, IL-6, VEGF and PIGF increased in HFB cells. The common cytokines in both cell lines were Ang-1, HGF, PIGF and VEGF. The mRNA and protein levels of the four cytokines were verified to increase by traditional RT-PCR and Western blotting in both cell lines after transfection of HPV-16 E6 and E7. Multiple pro-angiogenic cytokines could be stimulated by HPV-16 E6 and E7 protein both in cervical cancer cell line and normal human diploid cells. Anti-angiogenesis therapy may be effective alone or in combination with biologic means aimed at E6 and E7 in the treatment of cervical cancer.