Alpha-fetoprotein (AFP), present in 39-65% of patients with hepatocellular carcinoma (HCC), is widely used as a tumor marker to determine treatment effectiveness. Recent evidence suggests that AFP may be involved in HCC biology and is a determinant of clinical behavior. AFPep is an eight-amino acid cyclic peptide derived from domain III of AFP that retains the anti-estrotrophic property of its parent protein. This peptide has been proposed as a possible anticancer drug in breast cancer. Due to possible autocrine stimulation of AFP in HCC, the present study examined whether AFPep might modulate the growth of HCC cells in tissue culture. In these experiments, AFP-secreting HepG2 cells were conditioned with increasing concentrations of AFPep from 2x10-9M to 2x10-5M. Growth viability curves were subsequently determined using Trypan Blue exclusion. We report here that AFPep exerts pleiotropic and concentration dependent effects on the growth of HepG2 cells. During the first 7 days, AFPep mildly stimulated the growth of HepG2 cells at low concentration (2x10-9M) but consistently inhibited HepG2 growth at concentrations above 2x10-7M. With longer exposure to AFPep for 11 days, growth stimulatory effects dissipated at low concentration; only the growth inhibitory effect persisted. Our preliminary findings suggest that AFPep primarily inhibits HCC proliferation but may transiently stimulate growth at low concentrations. However, additional studies should be conducted to examine both AFP-secreting and -non-secreting HCC cells in vitro and other assay models.
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