Doxorubicin (DOX) is widely used in
cancer therapy of many
carcinomas types. Unfortunately, DOX is not sufficiently effective in many cases, and increasing the dosage of it is limited due to its systemic toxicity. A citrus
flavonoid hesperidin (HES) is proved to be potent
antioxidant and
protective agent against many diseases including
cancer. In this context, the objective of this study was to examine effect of HES along with DOX on solid Ehrlich
carcinoma (SEC) in mice. Forty male mice were divided into four equal groups (n = 10): control SEC, DOX, HES, and DOX + HES. HES (50 mg/kg
body weight orally) was given day after day for 16 days along with DOX (4 mg/kg
body weight i.p. injection) for 5 cycles every 4 days in ESC-inoculated mice. After 20 days,
tumor volume,
tumor weight, survival rate,
tumor glutathione,
nitric oxide content, and serum
glutathione were determined.
Tumor tissue was examined for histopathological and immunohistochemical study for p53 and
VEGF.
Tumor resistance for mdr1a gene was assessed in
tumor tissue by RT-PCR. HES induced significant increase in tissue and serum
glutathione with significant decrease in
tumor volume and
tumor weight. A possible role of HES to modulate gene expression of mdr1a in
tumor tissue was established. In addition, HES alleviated the histopathological changes with significant decrease in p53 and
VEGF expression. The use of HES as adjuvant
therapy with DOX would enhance the therapeutic efficacy and alleviate the resistance to DOX in treatment of solid
tumors.