Bruton’s Tyrosine Kinase (BTK) Inhibitor (Ibrutinib)-Suppressed Migration and Invasion of Prostate Cancer

Zhen Zhu,1,* Lanlan Ling,2,* Lezhong Qi,1 Yue Chong,3 Li Xue4 1Department of Urology, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 2Health Management Center, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 3Department of Urology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Urology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li XueDepartment of Urology, Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwulu Road, Xi’an, Shaanxi 710004, People’s Republic of ChinaTel/Fax +86-29-87679533Email xueli1979@xjtu.edu.cnIntroduction: Bruton’s tyrosine kinase (BTK) inhibitors have long been known in the treatment of B-cell malignancies. Recently, BTK inhibitors have also become promising novel treatment reagents for prostate cancer. The current study was designed to investigate expression of BTK in prostate cancer tissues in comparison with benign hyperplasia and effect of BTK inhibitor on prostate cancer cell proliferation, migration and invasion.Methods: BTK expression was assessed by immunohistochemistry; migration and invasion prostate cancer cell lines (DU145 and PC3) were assessed by Transwell migration and wound-healing assay; cancer cell proliferation was assessed using MTT assay kit; expression of matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) was assessed by immunoblotting.Results: Strong expression of BTK was detected in the prostate cancer tissues, especially in the tumors from prostate cancer patients with bone metastasis. BTK inhibitor (Ibrutinib) significantly inhibited cell proliferation, migration and invasion of prostate cancer cells as well as protein synthesis of MMP-2 and MMP-9 by the tumor cells. Overexpressing BTK could partially but significantly block the inhibitory effect of Ibrutinib on cell proliferation, migration and invasion, and protein synthesis of MMP-2 and MMP-9 of the cancer cells.Conclusion: These findings suggested that BTK could serve as not only a biomarker but also a therapeutic target for the prostate cancer and that Ibrutinib may be applied as a therapeutic drug for the prostate cancer.Keywords: Bruton’s tyrosine kinase, BTK, prostate cancer, matrix metalloproteinase, MMP