Perfluorooctanoic Acid Stimulates Ovarian Cancer Cell Migration,Invasion Via ERK/NF-?B/MMP-2/-9 Pathway

Background:PFOA(perfluorooctanoic acid)is a chemical product widely used in the manufacture of handmade products.It is also one of the persistent pollutants in the environment.The presence of PFOA can be detected in daily drinking water and even in human serum.In recent years,more and more studies have found that PFOA exposure is closely related to the occurrence of many diseases,including cancer related diseases.However,the related and possible molecular mechanisms of PFOA and the development of ovarian cancer are still not elucidated.Ovarian cancer,as one of the most common gynecologic malignant tumors,keeps a high mortality rate because of its incidious onset,rapid diffusion,and lack of the early effective screening and diagnosis methods.Most of the time,the cancer has already reached the late stage when diagnosed,so that the treatment effect of ovarian cancer is poor and the five-year survival rate is low.Therefore,in addition to actively looking for more specific and sensitive early screening indicators and further improving the treatment of ovarian cancer,we should try to reduce the exposure of ovarian cancer in risk factors and reduce the incidence of the disease.The aim of this study was to investigate the effects of PFOA exposure on ovarian cancer and its possible molecular mechanism of promoting invasion and metastasis of cancer cells.Method:The human epithelia ovarian cancer cell line A2780 was cultured in vitro,and the different concentrations of PFOA were used for the same time.The effects of different concentrations of PFOA on the proliferation,invasion and metastasis of A2780 cell line were detected by CCK-8,Transwell and scratch test,and the optimum experimental concentration was determined.The effects of 100nM PFOA on cell invasion and metastasis were investigated by Western blot and RT-PCR,combined with ERK1/2 inhibitor U0126+PFOA,NF-kappa B inhibitor JSH-23+PFOA co acting cells,and the possible molecular mechanism of promoting ovarian cell invasion and metastasis were further analyzed.Result:PFOA exposure had no significant effect on proliferation while it can significantly enhanced ovarian cancer cell migration and invasion.In addition,the expression of MMP-2/-9,a marker of cell invasion,was significantly increased,and the effect was significant at a drug concentration of 100 nM.Under the effect of 100nM PFOA,ERK1/2 pathway was activated,and ERK phosphorylation began to increase 3 hours after PFOA treatment,which was consistent with increased nuclear import of NF-?B and the up-regulation of MMP-2/9 expression.Under short-term PFOA,ERK phosphorylation was found to increase after 15 min of exposure to PFOA while activation of NF-?B were found to increase later,about 2h after exposure.The ERK1/2 inhibitor U0126 and NF-?B inhibitor JSH-23 were added in advance.After blocking the ERK1/2 pathway,activation of NF-?B was inhibited and the expression of MMP-2/-9 was down-regulated,which also reversed the PFOA-related increased migration and invasion of ovarian cancer cells.Inhibition of NF-?B activation also counteracted the potentiation of MMP-2/9 expression enhancement and ability of invasion and metastasis.Conclusion:PFOA upregulates MMP-2/-9 expression via ERK/NF-?B pathway,enhances ovarian cancer cell migration and invasion,and promotes the development of ovarian cancer.