Tetrandrine reverses epithelial-mesenchymal transition in bladder cancer by downregulating Gli-1

Zhang,Yongjian; Liu,Wei; He,Wenbo; Zhang,Yuanyuan; Deng,Xiuling; Ma,Yanmin; Zeng,Jin; Kou,Bo

doi:10.3892/ijo.2016.3415

Tetrandrine reverses epithelial-mesenchymal transition in bladder cancer by downregulating Gli-1

Authors:
- Yongjian Zhang
- Wei Liu
- Wenbo He
- Yuanyuan Zhang
- Xiuling Deng
- Yanmin Ma
- Jin Zeng
- Bo Kou
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Affiliations: Department of Cadiovascular Sugery, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China , Department of Burn and Plastic Surgery, Xi'an Central Hospital, Xi'an, Shaanxi 710061, P.R. China, Department of Reproductive Medicine, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: March 3, 2016 https://doi.org/10.3892/ijo.2016.3415
Pages: 2035-2042

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Abstract

Hedgehog (Hh) signaling pathway is considered to play a crucial role in vertebrate development and carcinogenesis. Additionally, epithelial-mesenchymal transition (EMT) is a cellular process during which epithelial cells become mesenchymal-appearing cells, facilitating cancer metastasis and invasion. Accumulating evidence has indicated that the Hh signaling pathway could potentiate the epithelial-mesenchymal transition (EMT). In the present study, we demonstrated that tetrandrine, a bisbenzylisoquinoline alkaloid isolated from Stephaniae, exerts its anti-metastatic ability in bladder cancer cells by regulating GLI family zinc finger 1 (Gli-1), a key factor of Hedgehog signaling pathway. In our study, we confirmed that tetrandrine could impede migration and invasion in bladder cancer 5637 and T24 cells. Additionally, tetrandrine reverses EMT by increasing the expression of E-cadherin and reducing the N-cadherin, vimentin and Slug expression in a dose-dependent manner. Interestingly, tetrandrine also decreases mobility and reduces the expression of Gli-1 in bladder cancer cells. Moreover, we verified that tetrandrine inhibits metastasis and induces mesenchymal-epithelial transition (MET) of bladder cancer through downregulation of Gli-1, which could be partially reversed by Gli-1 overexpression. In conclusion, our findings show that tetrandrine inhibits migration and invasion, and reverses EMT of bladder cancer cells through negatively regulating Gli-1. It indicates that Gli-1 may be a potential therapeutic target of tetrandrine against bladder cancer.

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