β-Elemene inhibits TGF-β1-induced EMT and invasion of cervical cancer cells through mediating β-catenin/TCF7/Sox2 signaling pathway

1. Abstract
1.1 Aims: The aim of this study was to investigate the effect and mechanism of β-elemene on TGF-β1-induced EMT, the migration and invasion in cervical cancer.
1.2. Methods: Firstly, we investigated the expression of TGF-β1 and β-catenin by immunohistochemistry and determined their prognostic values in the cervical cancer. Then EMT model was established by stimulating SiHa and HeLa cells with TGF-β1 and further explore the mechanism of β-elemene on TGF-β1-induced EMT, migration and invasion of cervical cancer cells.
1.3. Results: The results showed that TGF-β1 and β-catenin was overexpressed in cervical cancer tissues, and was positively correlated with FIGO staging, grade, lymph vascular infiltration and nodal metastasis, Besides, TGF-β1 and β-catenin overexpression predicted lower cumulative survival rate. TGF β1 (10 ng/ml) could increase the migration and invasion but β-elemene (40 μg/ml) could significantly inhibit TGF-β1-induced invasion and migration in SiHa cells and HeLa cells. TGF-β1 could increase the expression of β-catenin, Sox2, MMP-2, MMP-9 and Vimentin and reduce the expression of E-cadherin and promote β-catenin entry into the nucleus. However, after the treatment with β-elemene, the effect of TGF-β1 was reversed The results of immunoprecipitation showed that β-catenin could bind to Sox2 and β-elemene could decrease the binding of β-catenin to Sox2 in cervical carcinoma, indicating that β-elemene could inhibit β-catenin/TCF7/Sox2 signaling pathway to play an anti-tumor role.
1.4. Conclusion: In conclusion, we demonstrate that β-elemene inhibits TGF-β1-induced EMT, the migration and invasion of cervical cancer cells through mediating β-catenin/TCF7/Sox2 signaling pathway.