Inhibitory effect of topiramate on Lewis lung carcinoma metastasis and its relation with AQP1 water channel.
OBJECTIVE
To study the effect of topiramate on tumor metastasis and its relation with aquaporin 1 (AQP1) water channel.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Suppression of AQP1 water channel expression may be an important pathway for the inhibitory effect of topiramate on tumor metastasis.
Ma
Bing
B
Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100083, China.
Xiang
Yang
Y
Li
Tao
T
Yu
He-Ming
HM
Li
Xue-Jun
XJ
D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D018827:Carcinoma, Lewis Lung / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008168:Lung / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D000077236:Topiramate
C496021:Aqp1 protein, mouse; D020346:Aquaporins; D000077236:Topiramate; D051398:Aquaporin 1; D005632:Fructose; D002256:Carbonic Anhydrases