Silibinin attenuates TGF‑β1‑induced migration and invasion via EMT suppression and is associated with COX‑2 downregulation in bladder transitional cell carcinoma.

Abstract

Transforming growth factor (TGF)‑β1 is highly expressed in bladder transitional cell carcinoma (TCC) and is positively associated with tumor grade. TGF‑β1 signaling promotes cell metastasis by inducing epithelial‑mesenchymal transition (EMT), however, the underlying mechanisms are not fully understood. Our previous study demonstrated the anti‑metastatic effects of silibinin, a natural flavonoid derived from milk thistle, against TCC. The present study investigated the effects of silibinin on TGF‑β1‑induced EMT in TCC, focusing on the role of prostaglandin‑endoperoxide synthase 2 (COX‑2). Cell migration was determined by a wound healing assay and Transwell migration assay, and cell invasion was investigated using a Transwell invasion assay. Cell morphology was observed using an inverted microscope. Cell viability was evaluated by an MTT and cell counting assays. EMT markers were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting. Specific small interfering RNA was used to knockdown COX‑2 gene expression. TGF‑β1 promoted cell migration and invasion, induced EMT and upregulated the expression of COX‑2. COX‑2 knockdown attenuated TGF‑β1‑induced EMT, indicating that COX‑2 upregulation was essential for TGF‑β1‑induced EMT. Silibinin attenuated TGF‑β1‑induced migration and invasion by inhibiting EMT, and was associated with COX‑2 downregulation. TGF‑β1‑induced COX‑2 upregulation, which was inhibited by silibinin. In addition, TGF‑β1‑induced EMT was further inhibited when silibinin treatment was combined with COX‑2‑knockdown. The results suggested that silibinin may be a potential future treatment for metastatic TCC.

• Authors: Feng Li, Yi Sun, Jing Jia, Chao Yang, Xiaoshuang Tang, Ben Jin, Ke Wang, Peng Guo, Zhenkun Ma, Yule Chen, Xinyang Wang, Luke Chang, Dalin He, Jin Zeng
• Journal: Oncology reports (Oncol Rep) Vol. 40 Issue 6 Pg. 3543-3550 (Dec 2018) ISSN: 1791-2431 [Electronic] Greece
• PMID: 30272315 (Publication Type: Journal Article)

Chemical References

• Transforming Growth Factor beta1
• Silybin
• Cyclooxygenase 2
• PTGS2 protein, human

Topics

• Carcinoma, Transitional Cell (drug therapy, genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cyclooxygenase 2 (genetics, metabolism)
• Down-Regulation (drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Neoplasm Invasiveness
• Silybin (pharmacology)
• Transforming Growth Factor beta1 (pharmacology)
• Urinary Bladder Neoplasms (drug therapy, genetics, metabolism)