Investigation of the Role of Autophagy Related Proteins and PI3K/mTOR/Akt Pathway in Liver Cancer Treatment

The present study investigated the role of autophagy related proteins and PI3K/mTOR/Akt pathway. Treatment with graveoline for 48 h caused a significant (p < 0.05) increase in GFPLC3B labelling in Hep-3B and SK-Hep-1 cells. Treatment with graveoline at 0.5 to 32 mu M caused a dosedependent decrease in viability of both the tested cell lines. The viability of Hep-3B and SK-Hep-1 cells was decreased to 31 and 24%, respectively on treatment with 32 mu M graveoline compared to 100% in control. Expression of Atg5, Beclin and LC3B-II proteins showed a prominent increase in Hep-3B and SK-Hep-1 cells on treatment with 0.5 and 32 mu M graveoline. Graveoline treatment suppressed expression of pPI3K, pmTOR and pAkt proteins in Hep-3B and SK-Hep-1 cells. Graveoline treatment of Hep-3B and SK-Hep-1 cells at 0.5 and 32 mu M significantly elevated phosphorylation of ERK1/2 compared to untreated cells. Thus, graveoline inhibited liver cancer cell viability by increasing expression of autophagy-related proteins. Therefore, ERK1/2 activation and PI3K/mTOR/Akt pathway downregulation serves as a therapeutic target for various treatment strategies.