Aim: Berberine (BBR) acts as a tumor suppressor in different cancer cells. Our paper exerted efforts to discover the effect of BBR on cervical cancer.
Methods: Human cervical cancer cell lines SiHa and Ca Ski were treated with different concentrations of BBR. Cell viability, apoptosis, migration and invasion were detected by MTT assay, flow cytometry, wound healing assay, and Transwell assay, respectively. Expressions of Bcl-2-associated X protein (Bax), Bcl-2, cleaved (C) caspase-3 and epithelial-mesenchymal transition (EMT)-related proteins were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Keratin 17 (KRT17) expression in cervical cancer was identified by GEPIA2 and qRT-PCR. Rescue assay was then performed to assess the functional interaction between BBR and KRT17.
Results: Human cervical cancer cell viability, migration, and invasion were inhibited by BBR. BBR promoted cell apoptosis by increasing Bax and C caspase-3 expressions and decreasing Bcl-2 expression. Besides, BBR inhibited EMT in cells by decreasing the expressions of MMP-9, N-cadherin and Vimentin and increasing E-cadherin expression. Effects of BBR on cervical cancer cells were in a dose-dependent manner. Higher expression of KRT17 was found in cervical cancer SiHa and Ca Ski cells. BBR rescued the effects of KRT17 on promoting cell viability, metastasis, and the expressions of Bcl-2, MMP-9, N-cadherin and Vimentin, and suppressing apoptosis and the expressions of Bax, C-caspase-3 and E-cadherin.
Conclusion: BBR inhibited cervical cancer cell viability, metastasis and EMT but promoted cell apoptosis via suppressing KRT 17 expression.
Keywords: Berberine; Keratin 17; cervical cancer; epithelial-mesenchymal transition.