Aloperine Prevents Migration, Invasion, and Adhesion by Upregulating TIMP-4 in Human Bladder Cancer Cells

Background: Aloperine (ALO) is an important active component of quinolizidine alkaloids in Sophora flavescens A and Sophora alopecuroides L, and has effective anticancer activity against multiple cancers. However, the influence and mechanism of ALO on migration, invasion, and adhesion in bladder cancer cells remain unclear.

Objective: The aim of this study is to determine the anticancer effect of ALO on migration, invasion, and adhesion in bladder cancer cells and to investigate its potential TIMP-4-related mechanism.

Methods: Cell viability, cytotoxicity, wound healing, Transwell invasion, cell adhesion, real-time qPCR, western blot, and ELISA assays were performed to analyze the effect of ALO on migration, invasion, and adhesion in bladder cancer 5637 and UM-UC-3 cells. Furthermore, the anti-TIMP-4 antibody was used to explore the potential effect on ALO-inhibited bladder cancer cells.

Results: We have found that ALO significantly suppressed migration, invasion, and adhesion in bladder cancer cells. Furthermore, ALO could downregulate the expression of MMP-2 and MMP-9 mRNAs and proteins, and increase the expression of TIMP-4 mRNA and protein. Moreover, the anti- TIMP-4 antibody reversed the prevention of migration, invasion, and adhesion in ALO-treated bladder cancer cells.

Conclusion: The data in this study suggest that ALO suppressed migration, invasion, and adhesion in bladder cancer cells by upregulating the expression of TIMP-4.