Targeting Integrin-Linked Kinase Prevented Growth And Metastasis Of Bladder Cancer Cells

Objective The purpose of our study was to determine whether knockdown of ILK would inhibit cell growth, tumorigenesis and metastasis of bladder cancer.Methods We stably knocked down ILK in EJ cells. ILK siRNA led to inhibition of cell proliferate, migration, and invasion, as well as change of the cell morphology and realign of the microfilaments. We also demonstrated that ILK siRNA whether could inhibit phosphorylation of downstream signaling targets protein kinase B/Aktand GSK-3β. Using an EJ orthotopic and spontaneous metastatic animal model, BALB/C nude mice that were injected with the EJ–ILK siRNA and EJ cells.Results we stably knocked down ILK in EJ cells. ILK siRNA led to inhibition of cell proliferate, migration, and invasion, as well as change of the cell morphology and realign of the microfilaments. We also demonstrated that ILK siRNA could inhibit phosphorylation of downstream signaling targets protein kinase B/Aktand GSK-3βas well as reduce expression of MMP-2 and MMP-9, increase expression of RI, E-cadherin and nm23-H1 in vivo and vitro, which related cell proliferate, growth and metastasis. Using an EJ orthotopic and spontaneous metastatic animal model, BALB/C nude mice that were injected with the EJ–ILK siRNA cells showed a significant inhibition of the tumor growth with lighter tumor weight and lower density of microvessels than that in the control group mice (P<0.01), no metastasis was observed in the ILK downregulated group, whereas lung metastasis was detected in all mice of control groups.Conclusion The results highlight that ILK might play an important role in the development of bladder cancer by regulating key proteins, and could be served as a novel therapy target for human bladder cancer.