Pharmacology Department, Faculty of Medicine, Tanta University, Egypt.
Eur J Pharmacol. 2013 Aug 5;713(1-3):47-53. doi: 10.1016/j.ejphar.2013.04.049. Epub 2013 May 10.
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.
羟甲基戊二酰辅酶 A 还原酶是胆固醇合成的关键酶。胆固醇与许多类型癌症的发展之间存在关系。阿托伐他汀是一种降脂药物，可能在癌症治疗中发挥作用。此外，有报道称阿托伐他汀可降低癌细胞对许多化疗药物的耐药性。本研究旨在研究甲氨蝶呤（MTX）和阿托伐他汀单独和联合应用对小鼠实体 Ehrlich 癌（SEC）的影响。将 50 只 BALB/c 小鼠随机分为 5 组：未处理的对照组、SEC 组、SEC+MTX 组、SEC+阿托伐他汀组、SEC+MTX+阿托伐他汀组。测定肿瘤体积、组织谷胱甘肽还原酶（GR）、过氧化氢酶、丙二醛（MDA）、胆固醇和肿瘤坏死因子-α（TNF-α）。部分肿瘤进行组织病理学和免疫组织化学检查。与 SEC 组相比，MTX 或阿托伐他汀单独或联合应用可显著增加组织过氧化氢酶和 GR，显著减小肿瘤体积，降低组织 MDA、胆固醇和 TNF-α，并减轻组织病理学变化，同时增加 p53 表达和凋亡指数。综上所述，与 MTX 或阿托伐他汀单独应用相比，MTX 和阿托伐他汀联合应用对小鼠实体 Ehrlich 肿瘤的疗效更好。
