使用FXR 促動劑GW4064抑制人類膀胱腫瘤的遷移及入侵能力

顏維晨、查岱龍、高建璋、吳勝堂

國防醫學院三軍總醫院外科部泌尿外科

The FXR agonist GW4064 inhibits migration and invasion in human bladder cancer

Wei-Chen Yen, Dai-Lung Cha, Chien-Chang Kao, Sheng-Tang Wu

Division of Urology, Department of Surgery

Tri-Service General Hospital, National Defense Medical Center

Purpose:

GW4064 is a potent and selective nonsteroidal ligand for the nuclear bile acid receptor farnesoid X receptor (FXR; NR1H4). It had been utilized in research in cervical cancer, colorectal cancer, and breast cancer. In this study, we aimed to explore whether the FXR agonist GW4064 contributes to anticancer effects in human urothelial carcinoma.

Materials and Methods:

Two human urothelial carcinoma cell lines with distinct epithelial morphologies, RT4, T24 and human uroepithelial cell line SV-HUC-1, were obtained. One hundred RT4 and T24 cells per well were cultured in 6-well plates. The cells were incubated with DMSO or GW4064 for 9 days. The cells were fixed and stained. Finally, the colonies in each well were imaged and counted.

Results:

Exposure to GW4064 decreased the colony formation of RT4 and T24 cells. An inhibitory effect of GW4064 on both of these bladder cancer cell lines was observed in the wound healing migration assay. Moreover, GW4064 reduced the invasion of muscle-invasive T24 cells. The GW4064-induced decreases in migration and invasion were reversed by the proteasome inhibitor MG132 and the lysosome inhibitor NH4Cl, respectively.

Conclusion:

The FXR agonist GW4064 blocked the migration and invasion of human bladder cancer cells. In addition, treatment with a proteasome inhibitor and a lysosome inhibitor reversed the GW4064-induced inhibition of migration and invasion, respectively. Hence, GW4064 may be a potential therapeutic agent for human bladder cancer in the future.