Cytotoxic effects of antiglypican-3 against HepG2 cell line

For decades, various systemic therapies have been explored for the treatment of advanced hepatocellular carcinoma (HCC), the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Nevertheless, no satisfactory results have been obtained so far. Glypican-3 (GPC-3) is a cell-surface heparan sulfate proteoglycans (HSPGs) that emerged as a promising diagnostic marker as well as target for therapy. Therefore; we investigated antitumor activity of antiglypican-3 (antiGPC3), a specific antibody aginst GPC-3, against HepG2, human HCC, cell line. HepG2 cells were treated with AntiGPC3 at (5, 10 and 20 µg/ml). HepG2 cell proliferation was measured by MTT and lactate dehydrogenase (LDH) assays. GPC-3, HSPG and sulfatase-2 (SULF2) levels were measured by ELISA. Moreover, apoptosis was assessed by measuring Caspase-3 activity. We found that, antiGPC3 reduced HepG2 cells survival and showed cell cytotoxicity in a dose-dependent manner. In addition, antiGPC3 was able to increase the apoptosis measured by capase-3 activity in hepG2 cells. Finally, antiGPC3 restored HSPG level without affecting SULF2 in HepG2 cells. We can conclude that, antiGPC3 possesses cytotoxic effects, which can be partially explained by restoration of HSPGs and increase of caspase-3 apoptotic pathway. GPC-3 represents a promising target of HCC therapy.