Inhibition of TGF-β receptor I by siRNA suppresses the motility and invasiveness of T24 bladder cancer cells via modulation of integrins and matrix metalloproteinase

Background Urinary bladder transitional-cell carcinoma is still challenging because the mechanisms underlying the tumor progression are still largely unknown. Transforming growth factor β1 (TGF-β1) is considered a crucial molecule in the tumorigenesis of urinary bladder carcinoma. Many studies have indicated that it is also associated with epithelial–mesenchymal transition, angiogenesis, migration and metastases in many types of malignant tumors. Materials and methods We blocked the TGF-β signal pathway in T24 human bladder cancer cells with a siRNA (TsiRNA), which targets the TGF-β type I receptor and evaluated the effects of TGF-β1 and TsiRNA on the cell motility and invasiveness by Matrigel migration assay, wound-healing assay and Matrigel invasion assay. RT-PCR and Western blotting analysis were used to examine the effects of TGF-β1 and TsiRNA on the expression of TGFBRI and genes, which are related to tumor migration and invasion. Results While exogenous TGF-β1 enhanced the migration and invasion of T24 cells, TsiRNA significantly suppressed them. RT-PCR and Western blotting analysis revealed that TsiRNA could downregulate both the expression of α3, β1 and α2 integrin subunits and the activity of matrix metalloproteinase 9 enhanced by exogenous TGF-β1. Conclusion Our study suggested that inhibition of TGF-β1 signaling pathway by siRNA could be beneficial in the treatment of patients with metastatic bladder cancer.