Antiangiogenic and Proapoptotic Activities of Atorvastatin and Ganoderma lucidum in Tumor Mouse Model via VEGF and Caspase-3 Pathways

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Abstract
Background: The statin drug Atorvastatin (AT) used for cholesterol reduction and Ganoderma lucidum (Gl) mushroom extract exhibited satisfactory antitumor activities towards various types of cancer. Objective: The present study was designed to evaluate the apoptotic and antiangiogenic effects of Atorvastatin and/or Ganoderma lucidum against Ehrlich solid tumor inoculated in female mice. Materials and Methods: Atorvastatin (AT) or/and Ganoderma lucidum (Gl) extract were administered to mice bearing tumor alternatively for 28 days after 10 days of tumor cells inoculation. Mice were divided into 5 equal groups as follows: Control (C): Normal mice, Ehrlich (E): mice injected in thigh with EAC cells, (E+AT): mice bearing solid tumor that received an intraperitoneal dose of Atorvastatin (10 mg/kg). Group (4): (E+Gl): mice bearing solid tumor that received an oral dose of Ganoderma lucidum (28 mg/kg) Group (5): (E+AT+Gl): mice bearing solid tumor that received intraperitoneal dose of Atorvastatin and oral dose of Ganoderma lucidum. Results: showed that administration of Atorvastatin and/or Ganoderma lucidum to mice bearing tumor, reduced tumor size, increased MDA level and decreased GSH, SOD and CAT levels in tumor tissues. Histopathological study showed high attenuation in tumor cells associated with antiangiogenesis illustrated by extravasation of blood vessels between tumor cells. Immunohistochemical study demonstrated high reduction of the angiogenic marker Vascular endothelial growth factor (VEGF) with remarkable increase of the apoptotic protein markers cytochrome-c and caspase-3. Conclusion: Atorvastatin and Ganoderma lucidum may have anticancer, apoptotic and antiangiogenic activities by reducing tumor growth in Ehrlich solid tumor. Their antitumor effect is exerted through the antiangiogenesis effect in tumor cells which is confirmed by the decrease of the angiogenic marker (VEGF protein) as well as by inducing significant increase in the apoptotic protein markers cytochrome-c and caspase-3. It is noticeable that the antitumor activity is ameliorated by the combination of the two treatments.

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