Evaluation of antiglypican-3 therapy as a promising target for amelioration of hepatic tissue damage in hepatocellular carcinoma

    loading  Checking for direct PDF access through Ovid


In Egypt, hepatocellular carcinoma (HCC) was predicted to continue to rise over the next few decades causing a national problem. Meanwhile, glypican-3 (GPC3), a highly expressed glypican, has emerged as a potential target for HCC immunotherapy. Therefore, we aimed to identify the impact of blocking GPC3 on liver damage in HCC as well as a possible mechanism. Fifty four HCC patients, 20 cirrhotic patients and 10 healthy subjects were recruited. Serum levels of GPC3, sulfatase-2 (SULF-2), heparan sulfate proteoglycan (HSPG), insulin-like growth factor-II (IGF-II) were measured by ELISA. In parallel, HCC was induced in 40 male Sprague-Dawley rats in presence/absence of antiGPC-3. Liver impairment was detected by investigating liver sections stained with hematoxylin/eosin and serum α-fetoprotein (AFP). Liver homogenates of GPC3, SULF-2, and HSPG were measured by ELISA. Gene expression of caspase-3 and IGF-II were assayed by RT-PCR. HCC patients showed significant elevated serum levels of GPC3, IGF-II and SULF-2 accompanied by decreased HSPG. However, treatment of HCC rats with antiGPC-3 significantly reduced serum AFP and showed nearly normal hepatocytes. In addition, antiGPC-3 significantly reduced elevated liver homogenates protein levels of GPC3 and SULF-2 and gene expression of IGF-II and caspase-3. antiGPC-3 restored the reduced hepatic HSPG. antiGPC-3 showed anti-tumor activity as well as hepatoprotective effects. antiGPC-3-chemoprotective effect can be explained by forced reduction of IGF-II expression, restoration of HSPGs, deactivation of SULF-2 and reduction of gene expression of caspase-3. Targeting GPC3 is a promising therapeutic approach for HCC.

Related Topics

    loading  Loading Related Articles