Effect of atorvastatin and methotrexate on solid Ehrlich tumor

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...

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Published in:	European journal of pharmacology Vol. 713; no. 1-3; pp. 47 - 53
Main Authors:	Kabel, Ahmed M., Abdel-Rahman, Mohamed Nabih, El-Sisi, Alaa El-Din E., Haleem, Mahmoud Said, Ezzat, Nadia M., El Rashidy, Mohamed A.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 05-08-2013
Subjects:	Animals Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - therapeutic use Antioxidants - metabolism apoptosis Apoptosis - drug effects Atorvastatin Atorvastatin Calcium carcinoma Carcinoma, Ehrlich Tumor - drug therapy Carcinoma, Ehrlich Tumor - enzymology Carcinoma, Ehrlich Tumor - metabolism Carcinoma, Ehrlich Tumor - pathology catalase Catalase - metabolism cholesterol Cholesterol - metabolism Ehrlich Glutathione Reductase - metabolism glutathione-disulfide reductase Heptanoic Acids - administration & dosage Heptanoic Acids - therapeutic use histopathology Immunohistochemistry Male malondialdehyde Methotrexate Methotrexate - administration & dosage Methotrexate - therapeutic use Mice Mice, Inbred BALB C Mouse Neoplasm Transplantation Pyrroles - administration & dosage Pyrroles - therapeutic use tumor necrosis factor-alpha Tumor Necrosis Factor-alpha - metabolism Atorvastatin Mouse Methotrexate Ehrlich
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Summary:	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.
Bibliography:	http://dx.doi.org/10.1016/j.ejphar.2013.04.049 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-2999 1879-0712
DOI:	10.1016/j.ejphar.2013.04.049