Targeting Alpha-fetoprotein Represses the Proliferation of Hepatoma Cells Via Regulation of the Cell Cycle

Background: AFP is a biomarker for primary liver cancer, yet little is known about its effect in the pathogenesis of hepatoma. We examined how AFP modulates the proliferation of hepatoma cells.

Methods: Recombinant adenovirus expressing siRNA against AFP was created. The repression of cell proliferation in vitro and growth of hepatoma in vivo were examined by colony formation assay and tumor xenograft in SCID mice, respectively. Cell cycle was assayed by flow cytometry. Expression profile was determined by microarrays.

Results: siRNA targeting reduced expression of AFP specifically and markedly inhibited the proliferation of hepatoma cells. Local treatment using Adv-AFPsiRNA caused significant repression of the growth of hepatoma derived HepG2 cells in xenograft in SCID mice. Knockdown of AFP resulted in an obvious delay in the G(1)/S transition of cell cycle, but did not affect apoptosis in HepG2 cells. Some genes related to the cell cycle, including SKP2, Cyclin D1, Csk and EBAG9 were identified.

Conclusions: The endogenous AFP is a critical determinant of the growth of hepatoma cells, which functions by regulating the cell cycle. This study suggests that targeting of AFP with siRNA could be a potential therapeutic approach for hepatoma.