Study the Radio sensitization of Artesunate by Targeting Stemness and Hypoxia Markers on Solid Ehrlich Tumor Implanted in Mice

Abstract

Background: Cancer remains the main cause of death worldwide. Aim: This study was to investigate the antitumor potentiality and radio sensitizing effect of artesunate in combination with ionizing radiation on the Ehrlich solid carcinoma (ESC). Material and Methods: This study included 8 groups, each group included 8 Ehrlich solid carcinoma (ESC) bearing mice as follows, Group I: untreated ESC bearing mice as control group. Group II: Mice irradiated with a single dose (6Gy). Group III: Mice treated with artesunate alone (50mg/kg/day). Group IV: Mice treated with the combination of a single dose of IR (6Gy) and artesunate (50mg/kg/day). Group V: Mice treated with artesunate alone (100 mg/kg/day). Group VI: Mice treated with the combination of a single dose of IR (6Gy) and artesunate (100 mg/kg/day). Group VII: Mice treated with artesunate alone (200mg/kg/day). Group VIII: Mice treated with the combination of a single dose of IR (6Gy) and artesunate (200mg/kg/day). CD44, ALDH1A1, VEGF and HIF-1-α in tissue homogenate were measured by ELISA. P53 was investigated using Immunohistochemistry. Results: Tumor inhibition rate increased and tumor volume decreased in ESC, indicating that artesunate had anti-proliferative effects. Artesunate induced apoptosis through increased p53 expression. The combination of artesunate with IR significantly elevated tumor damage caused by ionizing radiation. Artesunate induces hypoxia and increases CSC makers in dose dose-dependent manner. Conclusion: Artesunate may be used as a potent anti-tumor agent against ESC and has radio sensitizing effects, particularly at 200 mg/kg dose by inducing apoptosis. Artesunate induces hypoxia which leads to increased CSCs markers