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

ABSTRACT

BACKGROUND: Urinary bladder transitional-cell carcinoma is still challenging because the mechanisms underlying the tumor progression are still largely unknown. Transforming growth factor beta1 (TGF-beta1) 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-beta signal pathway in T24 human bladder cancer cells with a siRNA (TsiRNA), which targets the TGF-beta type I receptor and evaluated the effects of TGF-beta1 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-beta1 and TsiRNA on the expression of TGFBRI and genes, which are related to tumor migration and invasion. RESULTS: While exogenous TGF-beta1 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 alpha3, beta1 and alpha2 integrin subunits and the activity of matrix metalloproteinase 9 enhanced by exogenous TGF-beta1. CONCLUSION: Our study suggested that inhibition of TGF-beta1 signaling pathway by siRNA could be beneficial in the treatment of patients with metastatic bladder cancer.