CD73 molecule inhibitor upregulates miR16 expression in experimental glioblastoma and inhibits angiogenesis by targeting VEGF

BackgroundThe function of CD73, an enzyme that is involved in adenosine (ADO) generation, in glioblastoma development has been demonstrated however the details of its molecular mechanisms are not realized nevertheless. MethodsDue to the significance of angiogenesis in cancer progression, invasion, and metastasis, we intended to evaluate the impact of CD73 inhibition by adenosine 5′-(α, β-methylene) diphosphate (APCP) on the angiogenesis process of experimental orthotopic glioblastoma at mRNAs, microRNAs, and proteins levels. ResultsAccording to the real time-PCR findings, CD73 inhibition decreased glioblastoma angiogenesis by reducing vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-alpha (HIF-1α) expression. Also, immunohistochemical staining showed that this treatment protocol attenuated the expression of VEGF and CD31. Moreover, APCP treatment in the glioblastoma model rats significantly increased miR-16 expression, although there is not observed significant change in expression in miR-29A. Treatment did not induce systemic damage or significant body weight loss.Conclusion In conclusion, our findings indicate that CD73 inhibition can diminish tumor new vessel generation by inhibiting the molecules involved in this process, thereby CD73 may be a practical target and provide novel opportunities for improving the treatment of malignant brain tumors.