Effect of Combination between Methotrexate and Histone Deacetylase Inhibitors on Transplantable Tumor Model

Abstract

Solid Ehrlich carcinoma is an undifferentiated tumor used in tumor studies. Methotrexate is an antimetabolite used in treatment of cancer, autoimmune diseases and induction of abortion. Valproic acid is used as anticonvulsant and is under investigation for treatment of cancer. The aim of this work was to study the effect of each of methotrexate and valproic acid alone and in combination on solid Ehrlich tumor in mice. Fifty albino mice were divided into five equal groups: Control untreated group, solid Ehrlich carcinoma, solid Ehrlich carcinoma + methotrexate, solid Ehrlich carcinoma + valproic acid, solid Ehrlich carcinoma + methotrexate + valproic acid. Tumor volume, tissue catalase, glutathione reductase, malondialdehyde, cholesterol and tumor necrosis factor-α were determined. A part of the tumor was examined for histopathological and immunohistochemical study. Methotrexate or valproic acid alone or in combination induced significant increase in tissue catalase and glutathione reductase with significant decrease in tumor volume, tissue malondialdehyde, cholesterol and tumor necrosis factor-α and alleviated the histopathological changes with significant increase in p53 expression and apoptotic index compared to solid Ehrlich carcinoma group. The combination of methotrexate and valproic acid has a better effect than each of methotrexate or valproic acid alone against solid Ehrlich tumor in mice.