title: Effect of atorvastatin and methotrexate on solid Ehrlich tumor.
abstract: Hydroxymethyl glutaryl CoA reductase is the key enzyme in cholesterol synthesis. A relationship was found between cholesterol and the development of many types of cancer. Atorvastatin is a hypolipidemic drug that may have a role in treatment of cancer. Moreover, atorvastatin was reported to decrease the resistance of cancer cells to many chemotherapeutic agents. The aim of this work was to study the effect of each of methotrexate (MTX) and atorvastatin alone and in combination on solid Ehrlich carcinoma (SEC) in mice. Fifty BALB/c mice were divided into five equal groups: control untreated group, SEC, SEC+MTX, SEC+atorvastatin, SEC+MTX+atorvastatin. Tumor volume, tissue glutathione reductase (GR), catalase, malondialdehyde (MDA), cholesterol and tumor necrosis factor alpha (TNF-α) were determined. A part of the tumor was examined for histopathological and immunohistochemical study. MTX or atorvastatin alone or in combination induced significant increase in tissue catalase and GR with significant decrease in tumor volume, tissue MDA, cholesterol and TNF-α and alleviated the histopathological changes with significant increase in p53 expression and apoptotic index compared to SEC group. In conclusion, the combination of MTX and atorvastatin had a better effect than each of MTX or atorvastatin alone against solid Ehrlich tumor in mice.
authors.affiliation: Pharmacology Department, Faculty of Medicine, Tanta University, Egypt. drakabel@gmail.com
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Kabel
authors.forename: Mohamed Nabih
authors.initials: MN
authors.lastname: Abdel-Rahman
authors.forename: Alaa El-Din E
authors.initials: Ael-D
authors.lastname: El-Sisi
authors.forename: Mahmoud Said
authors.initials: MS
authors.lastname: Haleem
authors.forename: Nadia M
authors.initials: NM
authors.lastname: Ezzat
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: El Rashidy
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D006538:Heptanoic Acids; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D000069059:Atorvastatin; D002374:Catalase; D005980:Glutathione Reductase; D008727:Methotrexate