Topiramate exhibits anti-tumorigenic and metastatic effects in ovarian cancer cells

American Journal of Translational Research

Yajie Yin¹  Guangxu Xu²  Leslie H Clark³  Ziwei Fang⁴  Wenchuan Sun⁵ 

[1] Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, P. R. China;Department of Gynecology, Shanghai Jiaotong University Affiliated Sixth People Hospital South Campus, Shanghai, P. R. China;Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, P. R. China;Division of Gynecologic Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

关键词: Ovarian cancer;    carbonic anhydrases;    topiramate;    invasion;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Ovarian cancer is one of the leading causes of cancer related deaths among women worldwide, with an overall 5-year survival of only 30-40%. Carbonic anhydrases are up-regulated in many types of cancer and play an important role in tumor progression and metastasis. Carbonic anhydrase 9 has been implicated as a potential anti-tumorigenic target. Topiramate (TPM) is a potent inhibitor of carbonic anhydrase isozymes, including carbonic anhydrase 9, and has been shown to have anti-tumorigenic activity in several cancer types. Our goal was to evaluate the effect of TPM on cell proliferation and to identify possible mechanisms by which TPM inhibits cell growth in ovarian cancer. TPM significantly inhibited ovarian cancer cell proliferation and induced cell cycle G1 arrest, cellular stress and apoptosis through the AKT/mTOR and MAPK pathways. TPM also exerted anti-metastatic effects by decreasing the adhesion and invasion of ovarian cancer cells and affecting the expression of critical regulators of the epithelial-mesenchymal transition (EMT). Our findings demonstrate that TPM has anti-tumorigenic effects in ovarian cancer and is worthy of further exploration in clinical trials.

【 授权许可】

CC BY-NC