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

乙酰唑胺抑制肿瘤转移及荷瘤小鼠肺相关蛋白质的表达(英文)

作　　者：项阳[1] 马兵[1] 李涛[1] 于和鸣 李学军 

机构地区：[1]北京大学医学部药理学系,北京100083 [2]国家计划生育委员会科学技术研究所,北京中国100081

出　　处：《Acta Pharmacologica Sinica》2002年第8期745-756,共12页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China,№ 39770286 and 30171090.

摘　　要：AIM: 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 metasta-sis 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-1·d-1 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 AQP, 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. CONCLUSION: Acetazolamide can suppress tumor metastasis, at least in part, by inhibiting the expression of AQP1. AQP1 and actin-cytoplasmic may be new prognos-tic molecules as well as new therapeutic targets for the prevention and treatment of metastatic tumor.目的:研究乙酰唑胺对肿瘤转移的抑制及相关蛋白质的表达.方法:以 Lewis肺癌为肿瘤转移模型,观察乙酰唑胺对肿瘤转移的影响;用SDS/PAGE、 Western blot、IEF和肽质量指纹谱的方法观察相关蛋白质的变化.结果:乙酰唑胺可以显著抑制肿瘤转移,肺转移抑制率为83.9％.荷瘤小鼠肺组织中水通道蛋白-1和肌动蛋白表达明显增高,用乙酰唑胺治疗后水通道蛋白-1表达降低.结论:乙酰唑胺具有抗肿瘤转移作用,其机制可能与抑制水通道蛋白-1的表达有关;水通道蛋白-1和肌动蛋白可望成为肿瘤肺转移诊疗的新靶标.

关 键 词：ACETAZOLAMIDE neoplasm metastasis AQUAPORINS ACTIN 

分 类 号：R73-3[医药卫生—肿瘤]