Role Of CCL18, CXCL1and IL8in Tumour Growth And Metastasis Of Ovarian Cancer In Vivo

Objective The pelvic peritoneum metastasis was widely happened in advanced epithelial ovarian cancer, and surgical excision of ovarian lesion s was difficult, which are leading cause of mortality. Therefore, finding t he correlative factors of metastasis for ovarian cancer and taking effective measures for target therapy have become a key of improving the efficac y. In our previous studies it has been shown that CCL18, CXCL1and IL8were regulated patients’serum of ovarian cancer and they could obviou sly promote the growth and invasion of ovarian cancer cells in vitro. In t his study, we use nude mouse xenograft models to invatigate the roles of CXCL1, CCL18and IL-8in ovarian cancer growth and metastasis.Methods Building over expressed chemokine (CXCL1, CCL18and t hree of IL-8clipping isoforms-IL8-1, IL8-2, IL8-3) gene ovarian cancer cell lines carried with GFP fluorescence labeling using PWPI lentivirus eu karyotic cell expression system. Establishing an subcutanous xenograft mo del and orthotopic xenograft model of human ovarian cancer in the nude mice using these cell lines, which can help to observe the influence of c hemokine CXCL1, CCL18and IL-8on tumour growth and metastatsis. T he expression of MMPs and VEGFs genes were measured by Real-time f luorescent quantitative PCR. Western blot and immunohistochemistry detec ted the expression of CXCL1, CCL18and IL-8proteins.Results Real-time fluorescent quantitative PCR assay showed that ex pression level of CXCL1, CCL18and IL8gene could be improved signif icantly after SKOV3cells infected with recombinant lentiviral compared with the control group (P<0.05). Over expression of CXCL, CCL18and IL8proteins in these SKOV3cells were observed by western blot and i mmunohistochemistry. In the subcutanous xenograft model, IL8-1/SKOV3, IL8-2/SKOV3and CXCL1/SKOV3groups had evidently promoted the we ight of the tumor compared with the control groups (P<0.05). CCL18/S KOV3and IL8-3/SKOV3groups were not significant compared with the control groups (P>0.05). IL8-1/SKOV3, IL8-2/SKOV3and CCL18/SKOV3groups orthotopic xenograft model presented with bowel and spleen met astases at2weeks after surgery, at the same time tumour transplantation speed increased obviously in enterocoelia compared with CXCL1/SKOV3groups and the control groups. Expression of VEGFC, MMP1, MMP7, M MP11, MMP12, and MMP15genes were all improved significantly in theIL8-2/SKOV3group compared with the control groups (P<0.05) by qRT-PCR assay. The expression levels of VEGFC, MMP1, MMP7, MMP11a nd MMP15genes were improved significantly in the CCL18/SKOV3grou p compared with the control groups (P<0.05).Conclusion The transplant tumor model in vivo showed that the expression of CCL18is positively correlated with the metastasis of ovarian cancer. CXCL1mainly promote the tumor cell growth, but it can’t promote the tumor cell metastasis. IL-8can promote the tumor growth and metastasis simultaneously.