Fraxetin suppresses the proliferation, migration, and invasion of ovarian cancer cells by inhibiting the TLR4/STAT3 signaling pathway

Abstract

Background

Little therapeutic effect can be exerted on malignant ovarian cancer at the terminal period. Traditional Chinese medicine (TCM) has been a potential way for the treatment of various diseases. In this research, we probed into the potential curative effect of Fraxetin (FXT), a TCM monomer, on ovarian cancer.

Methods

Ovarian cancer cells were treated with FXT at different concentrations for 12 h, or pretreated by 0.5 μM of colivelin, a STAT3 activator, for 1 h and then treated with 80 μM of FXT for 12 h. The viability of ovarian cancer cells was measured by MTT assay, and the cell colony number was counted after colony formation assay. Transwell assay was conducted for investigating the relationship between the FXT at different concentrations and the invasion as well as migration rates of ovarian cancer cells. The expressions of epithelial-to-mesenchymal transition (EMT)-associated markers and TLR4/STAT3 signaling pathway-related proteins in ovarian cancer cells after the treatment of FXT were measured by western blot.

Results

FXT inhibited the viability, invasion, migration, and proliferation of SKOV3 and SW626 cells and suppressed EMT, but colivelin reversed the impacts of FXT. FXT also suppressed the expressions of N-cadherin, snail, vimentin, TLR4, phosphorylated (P)-STAT3, cyclin D1, and C-myc, whilst promoting that of E-cadherin by inhibiting the activation of TLR4/STAT3 signaling pathway.

Conclusion

FXT exerts a therapeutic effect on ovarian cancer by repressing the TLR4/STAT3 signaling pathway. With the accumulating concentrations of FXT, the therapeutic effect becomes more and more obvious.

Keywords:

• Epithelial-to-mesenchymal transition
• Fraxetin
• ovarian cancer
• TLR4/STAT3 signaling pathway
• traditional Chinese medicine

Author contributions

Substantial contributions to conception and design: Ruhu Xu.

Data acquisition, data analysis and interpretation: Yingdan Ruan, Lan Zhang, Yating Gu, Mingming Liu.

Drafting the article or critically revising it for important intellectual content: Ruhu Xu.

Final approval of the version to be published: Ruhu Xu, Yingdan Ruan, Lan Zhang, Yating Gu, Mingming Liu.

Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved: Ruhu Xu, Yingdan Ruan, Lan Zhang, Yating Gu, Mingming Liu.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.