Acetazolamide suppresses tumor metastasis and related protein expression in mice bearing Lewis lung carcinoma.
OBJECTIVE
To study the suppressing effect of acetazolamide on tumor metastasis in vivo and observe the protein alteration of lung in mice bearing Lewis lung carcinoma.


METHODS
The functional role of aquaporin-1 (AQP1) was investigated in tumor tissues by SDS-PAGE and Western blot. The effect of acetazolamide on tumor metastasis was analyzed by Lewis-lung-carcinoma model. Differential protein was identified by SDS-PAGE, isoelectrofocusing (IEF) methods, and peptide mass fingerprinting (PMF).


RESULTS
Acetazolamide (40 mg/kg/d po for 21 d) dramatically reduced the numbers of lung metastasis after sc inoculating Lewis lung carcinoma. The inhibition rate of lung metastases was 83.9 %. Simultaneously, the AQP1 protein level and actin-cytoplasmic in lungs containing metastatic tumor deposits were found to be higher than that in the normal tissue. After treated with acetazolamide for 21 d, the expression of AQP1 was obviously inhibited.


CONCLUSIONS
Acetazolamide can suppress tumor metastasis, at least in part, by inhibiting the expression of AQP1. AQP1 and actin-cytoplasmic may be new prognostic molecules as well as new therapeutic targets for the prevention and treatment of metastatic tumor.
Xiang
Yang
Y
Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100083, China.
Ma
Bing
B
Li
Tao
T
Yu
He-Ming
HM
Li
Xue-Jun
XJ
D000086:Acetazolamide / Q000494:pharmacology*; D000199:Actins / Q000096:biosynthesis; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D051398:Aquaporin 1; D020346:Aquaporins / Q000096:biosynthesis*; D018827:Carcinoma, Lewis Lung / Q000378:metabolism / Q000473:pathology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control
D000199:Actins; D000970:Antineoplastic Agents; C496021:Aqp1 protein, mouse; D020346:Aquaporins; D051398:Aquaporin 1; D000086:Acetazolamide