Doaa Ali Abdelmonsif
Alexandria University Alexandria, Egypt
Title: Targeting AMPK, mTOR and βCatenin by Combined Metformin and Aspirin Therapy in HCC: AnAppraisal to Egyptian HCC Patients
Biography
Biography: Doaa Ali Abdelmonsif
Abstract
Hepatocellular carcinoma (HCC) is an expanding health problem with a great impact on morbidity and mortality both in Egypt and worldwide. Recently, metformin and aspirin showed a potential anticancer effect on HCC although their mechanism(s) isn't fully elucidated. To investigate the anti-proliferative effects of combined metformin/ aspirin treatment against HCC, HepG2 cells were exposed to increasing concentrations of metformin, aspirin and combined treatment, and MTT assay was performed. Caspase-3 activity, cell cycle analysis, protein expression of phosphorylated AMP-activated protein kinase (pAMPK) and mammalian target of rapamycin (mTOR) proteins were assessed. Furthermore, the expression and localization of β-catenin protein was assessed by immunocytochemistry (ICC). Finally, protein expression of pAMPK, mTOR and β-catenin was assayed in Egyptian HCC and cirrhotic tissue specimens. Results showed that metformin/aspirin combined treatment had a synergistic effect on cell cycle arrest and apoptosis induction via down-regulation of AMPK activation and mTOR protein expression. Additionally, metformin/aspirin combined treatment enhanced cell-cell membrane localization of β-catenin expression in HepG2 cells, which might inhibit metastatic potential of HepG2 cells. In Egyptian HCC specimens, pAMPK, mTOR and β-catenin proteins showed a significant expression compared to cirrhotic controls. In conclusion, combined metformin/aspirin treatment could be a promising therapeutic strategy for HCC and specifically Egyptian HCC patients.