The highly relevant association between obesity and female cancer as well as free fatty acids (FFAs) increasing the risk of female cancer development have been shown in several epidemiological studies. Oleic acid (OA) is an abundant FFA in adipose tissue. It can promote metastatic ability of breast cancer through adjusting MMPs expression which was observed in previous studies. However, the effect of OA on the development of ovarian carcinoma still unclear.
In this study, we used an ovarian cancer cell lines, SKOV3, as a cell model to elucidate the relationship between OA and ovarian cancer. The cell viability effect of oleic acid treatment was detected by MTT assay. Metastatic ability of cancer cell was observed by Boyden chamber experiment. The highly potential target genes involved in this study were screened by microarray experiment. Antibody neutralization blocked specific receptor function and shRNA transfection were used to validate the signaling pathway of oleic acid in ovarian cancer.
The result of MTT assay revealed that OA didn’t have significant influence on cell viability. However, Boyden chamber assay showed that OA can increase migration and invasion ability of SKOV3 which related to metastatic potential of cancer cell. Urokinase-type plasminogen activator receptor (uPAR) was three times higher than control group in microarray assay. In our data, uPAR expression significantly increased at 6 hours after OA treatment and the effect of overexpression can last to 48 hours in both RNA and protein levels. After blocking uPA/uPAR signaling pathway with uPAR neutralization antibody, the number of cancer cell migrating through the chamber reduced. Furthermore, cancer metastatic ability such as migration and invasion was also inhibited by knockdown uPAR expression with shRNA.
The result of our study demonstrated that oleic acid might involve in SKOV3 metastasis via uPAR and uPA/uPAR signaling pathway. This finding is consistent with the observation of previous studies concerning uPAR to cancer metastasis and proliferation. Accordingly, our result provides a possible linkage between obesity and ovarian cancer aggressiveness.
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All authors have declared no conflicts of interest.