Acetazolamide suppresses tumor metastasis and related protein expression in mice bearing Lewis lung carcinoma. 2002

Yang Xiang, and Bing Ma, and Tao Li, and He-Ming Yu, and Xue-Jun Li
Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100083, China.

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.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009362 Neoplasm Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. Metastase,Metastasis,Metastases, Neoplasm,Metastasis, Neoplasm,Neoplasm Metastases,Metastases
D005260 Female Females
D000086 Acetazolamide One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337) Acetadiazol,Acetazolam,Acetazolamide Sodium, (Sterile),Acetazolamide, Monosodium Salt,Ak-Zol,Apo-Acetazolamide,Diacarb,Diamox,Diuramide,Défiltran,Edemox,Glauconox,Glaupax,Huma-Zolamide,Ak Zol,AkZol,Apo Acetazolamide,ApoAcetazolamide,Huma Zolamide,HumaZolamide
D000199 Actins Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle. F-Actin,G-Actin,Actin,Isoactin,N-Actin,alpha-Actin,alpha-Isoactin,beta-Actin,gamma-Actin,F Actin,G Actin,N Actin,alpha Actin,alpha Isoactin,beta Actin,gamma Actin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051398 Aquaporin 1 Aquaporin 1 forms a water-specific channel that is constitutively expressed at the PLASMA MEMBRANE of ERYTHROCYTES and KIDNEY TUBULES, PROXIMAL. It provides these cells with a high permeability to WATER. In humans polymorphisms of this protein result in the Colton blood group antigen. AQP-CHIP Protein,AQP1 Protein,Aquaporin 1 Protein,Aquaporin-CHIP,CHIP28 Protein,Channel-Forming Integral Membrane Protein Of 28 kDa,AQP CHIP Protein,Aquaporin CHIP,Channel Forming Integral Membrane Protein Of 28 kDa
D018827 Carcinoma, Lewis Lung A carcinoma discovered by Dr. Margaret R. Lewis of the Wistar Institute in 1951. This tumor originated spontaneously as a carcinoma of the lung of a C57BL mouse. The tumor does not appear to be grossly hemorrhagic and the majority of the tumor tissue is a semifirm homogeneous mass. (From Cancer Chemother Rep 2 1972 Nov;(3)1:325) It is also called 3LL and LLC and is used as a transplantable malignancy. Lewis Lung Carcinoma,Lung Carcinoma, Lewis

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