The protein profile of acetazolamide-treated sera in mice bearing Lewis neoplasm.
The aim of the present research is to analyze the proteome of neoplasm serum before and after treated with acetazolamide (20, 40, 80 mg kg(-1) d(-1) for 3 days p.o.). The Lewis lung carcinoma mice were used and carried out a comprehensive proteomic analysis by using the technologies of high-resolution two-dimensional polyacrylamide gel electrophoresis (2D PAGE) and mass spectrometry (MS). The results showed that the acetazolamide could dramatically reduce the lung metastasis and primary tumor growth. Its most potent inhibition rate on lung metastases was reach to 77.7% at the dose of 80 mg kg(-1) d(-1). The two dimension electrophoresis and software analysis reveal 393 protein spots in control gel, 385 protein spots were detected in treated gel and matched 209 protein spots with control gel, indicating that intensive changes had occurred during the process of treatment. Two obviously different spots were cut off from gel and for the peptide mass fingerprinting. Data base searching showed the two proteins' peptide much more mach with Histone H2B fragment and Ubc-like protein CROC1 fragment. The results suggest that acetazolamide has a strong anti-tumor and anti-metastasis effect on Lewis-lung-carcinoma. The mechanism may be related to its regulation on plenty of proteins, in particular, on upregulation of H2B and CROC-1 expression of postreplicational DNA repair related protein in serum.
Xiang
Yang
Y
Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100083, China.
Ma
Bing
B
Yu
He-ming
HM
Li
Xue-Jun
XJ
D000086:Acetazolamide / Q000008:administration & dosage / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001798:Blood Proteins / Q000032:analysis / Q000187:drug effects*; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control; D020543:Proteome
D000970:Antineoplastic Agents; D001798:Blood Proteins; D002257:Carbonic Anhydrase Inhibitors; D020543:Proteome; D000086:Acetazolamide