topiramate and Carcinoma--Lewis-Lung

Topiramate has been used in patients with brain tumors who develop epilepsy. In our previous research we found topiramate could inhibit tumor metastases of Lewis lung carcinoma in C57BL/6 mice. In this study we aimed to assess the antimetastatic activity of topiramate and determine its mechanism of action. After confirming the effects of topiramate on Lewis lung carcinoma in C57BL/6 mice, we assessed the mRNA expression of carbonic anhydrases II and IX, and the vascular endothelial growth factor (VEGF) distribution in tumor tissue. We studied the role of topiramate on primary angiogenesis using a chicken embryo chorioallantoic membrane angiogenesis model, and analyzed the protein profile of serum from mice treated with or without topiramate by two-dimensional electrophoresis. We found that topiramate significantly reduced the primary tumor growth (P<0.05) and the degree of damage to the lung alveoli caused by metastatic tumor deposits. The two-dimensional electrophoresis revealed changes that occurred with topiramate treatment and four down-regulated protein spots were clearly identified as tropomyosin, osteopontin, transthyretin, and serum amyloid A-1. The mRNA and protein expression of serum amyloid A-1, osteopontin and its receptor, integrin α(v)β(3) in tumor tissue were reconfirmed. The results suggest that topiramate has antitumor and antimetastatic effects on Lewis lung carcinoma. Its mechanism of action may be related to its inhibition of angiogenesis by down-regulation of osteopontin, VEGF and carbonic anhydrase II.

Topics: Animals; Antineoplastic Agents; Blood Proteins; Carbonic Anhydrase II; Carcinoma, Lewis Lung; Chorioallantoic Membrane; Down-Regulation; Female; Fructose; Gene Expression Regulation, Neoplastic; Integrin alphaVbeta3; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neovascularization, Pathologic; Osteopontin; Proteome; Proteomics; Pulmonary Alveoli; RNA, Messenger; Topiramate; Vascular Endothelial Growth Factor A

To study the effect of topiramate on tumor metastasis and its relation with aquaporin 1 (AQP1) water channel.. Lewis lung carcinoma metastatic model was used to determine the effect of topiramate on tumor growth and metastasis. Colorimetric estimation was used to investigate the action of topiramate on carbonic anhydrase (CA) activity. Western blotting and immunohistochemical analysis were used to study the influence of topiramate on AQP1 water channel expression in lungs or tumor tissues of mice bearing Lewis lung carcinoma.. Treatment with topiramate (120 mg/kg/d, ig for 20 d) reduced the growth of primary tumor significantly (P<0.05). Its inhibitory rate of metastasis was 81.25 %. Topiramate inhibited CA activity in lungs of mice in a dose-dependent manner. Topiramate apparently decreased AQP1 protein expression and immunostaining in lungs or in tumor microvessel endothelial cells of mice.. Suppression of AQP1 water channel expression may be an important pathway for the inhibitory effect of topiramate on tumor metastasis.

Topics: Animals; Aquaporin 1; Aquaporins; Carbonic Anhydrases; Carcinoma, Lewis Lung; Female; Fructose; Lung; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Topiramate