Abstract: Objective To investigate the effect of notch signaling pathway on bladder cancer drug resistance and invasiveness. Methods We observed the changes of growth and morphological of bladder cancer T24, 5637 and J82 cells which treated for 48 hours using γ-secretase inhibitor by inverted microscope; We detected the mRNA and protein levels of the EMT molecular markers, including E-cadherin, N-cadherin, Vimentin and Alpha-smooth muscle actin, by RT-PCR and Western blot in bladder cancer cells; Detected the changes of drug resistance and invasion respectively by MTT and Transwell in bladder cancer cells. Results After completely blocking the Notch signaling pathway, the inverted microscope showed that bladder cancer cells became smaller and more disperse; RT-PCR and Western blot showed the mRNA and protein levels of E-cadherin were up-regulated (P < 0.05), contrast, N-cadherin, Vimentin and Alpha-smooth muscle actin were down-regulated (P< 0.05); The proliferation of bladder cancer cells was significantly inhibited by MTT test; The number of through microporous membrane cells was significantly decreased (P < 0.05) by Transwell test. Conclusion The Notch signaling pathway is completely blocked that could inhibit the proliferation and EMT of bladder cancer cells and reduce drug resistance and invasion in bladder cancer cells，it suggests that drug resistance and invasiveness of bladder cancer can be changed by EMT which is regulated by notch signaling pathway.

Key words: bladder cancer, γ-secretase inhibitor, notch signal, EMT