Engagement of integrinß1 induces resistance of bladder cancer cells to mitomycin-C.

OBJECTIVE: To identify whether integrinß1 subunit is responsible for the resistance of bladder cancer cell to the therapeutic drug mitomycin-C (MMC), when grown on fibronectin (FN). MATERIALS AND METHODS: The expression of integrinß1 on bladder cancer T24 and 5637 cells was examined by the flow cytometer. The adhesion of cells to plates with the absence or presence of FN was determined. Analysis of apoptosis induced by MMC was assessed using the flow cytometer in combination with an integrinß1-blocking antibody or siRNA targeting the coding region of integrinß1. Western blot was used to study the expression change of integrinß1 and its downstream molecules. RESULTS: Bladder cancer T24 and 5637 cells express high level of integrinß1 (87.3% ± 2.3 and 90.1% ± 1.9, respectively). Cellular adhesion to FN was significantly reduced by the blocking of integrinß1. Blocking or silencing of integrinß1 significantly abolished the drug resistance of cells grown on FN to MMC (P <.05) and inhibited the activation of survival signals phosphoinositide-3 kinase (PI3-K)/Akt. CONCLUSION: Integrinß1-mediated cellular adhesion to FN confers drug resistance to MMC on bladder cancer cells. Knockdown of integrinß1 may abolish the drug resistance phenotype and sensitize bladder cancer cells to MMC.