Abstract:
Introduction: Short-chain fatty acids (SCFAs) have recently garnered considerable attention due to their anti-proliferative effect in various cancer types. However, the precise mechanisms underlying their inhibitory potential in ovarian cancer require further investigation.
Objectives: This study aims to explore the anti-metastatic properties of SCFAs by examining the effects of sodium butyrate (NaB) and sodium propionate (NaP) on the migration and invasion of ovarian cancer cells. It also seeks to evaluate their role in Epithelial-to-Mesenchymal Transition (EMT) regulation and the signaling pathways that underlie their effects.
Methodology: The two ovarian cancer cell lines, SKOV-3 and PA-1, were treated with NaB and NaP for 24h. The anti-migratory and anti-invasive effects of both compounds were evaluated using wound healing, transwell migration, and transwell invasion assays. Real-Time PCR and Western Blot were performed to assess the effects of NaB and NaP on the expression profile of key EMT-related markers. The MEK-ERK signaling pathway was assessed through the evaluation of the total and phosphorylated levels of the proteins by western blot. Results: NaB and NaP were able to significantly inhibit migration and invasion of SKOV-3 and PA-1 cell lines in a dose-dependent manner following 24h and 31h of treatment, respectively. Moreover, treatment with both compounds resulted in a decrease in mRNA and protein expression levels of the mesenchymal markers vimentin and beta-catenin. Unlike SKOV-3 cells, which demonstrated a decrease in E-cadherin and an increase in N-cadherin after treatment, the E-cadherin/N-cadherin profile in PA-1 treated cells exhibited an inverse pattern. Finally, our results revealed a significant decrease in the ratios of P-ERK/ERK and P-MEK/MEK following treatment.
Conclusion: Our study underscores the promising therapeutic potential of NaB and NaP, offering insights into their ability to inhibit migration and invasion by regulating EMT and deactivating MEK/ERK signaling in ovarian cancer.
