The Role Of Alpha Fetoprotein On Hepatocellular Carcinoma Resisting All Trans Retinoic Acid

Objective:Hepatocellular carcinoma(HCC)is a malignant tumor that endangers human health,and liver cancer is the third most common cause of cancer death.In recent years,there has been a slow rise in the recurrence and mortality of patients with liver cancer,this trend is closely related to drugs-resistance of HCC,so search for the drug-resistant molecular mechanism will provide an effective way to confront liver cancer.A large number of studies have shown that the alpha-fetoprotein(AFP)was able to interact with retinoic acid receptor(RAR)-β,and blocked the binding of all trans retinoic acid(ATRA)and RAR-β this led to liver cancer cells resistant the the role of ATRA.Many studies have shown that RAR-α,RAR-γ plays a different role in the development of liver cancer,and some studies have shown that RAR-γ is a oncogene.In the present study,we explored the association of AFP and RAR-α,RAR-γ,and the role of AFP on HCC cells resistance of ATRA.Methods: MTT method was applied to detect the effect of ATRA on the growth of HCC cells.DAPI stained was used to display that ATRA induced apoptosis of liver cancer cells.The distribution and co-location of AFP and RAR-α/γ,in liver cancer cells were observed by laser confocal microscopy,and the the neclues translocation of RAR-α/γ was observed by fluorescent microscopy.Inhibited expression of AFP in PLC and Bel 7402 cells was mediated by AFP-si RNA vector(si RNA-AFP923),and induce expression of AFP in HLE cells was transfected with AFP-expressed vector(pc DNA3.1-EGFP-afp).Western Blotting was used to analyze the expression of AFP,RAR-α/γ,survivin,Bcl-2 in HLE,Bel7402,and PLC.Results: The MTT results shown that ATRA could inhibit the proliferation of HCC,AFP was able to antagonism inhibited effect ATRA on the proliferation of liver cancer cells.The DAPI stained indicates that ATRA could promote the apoptosis of liver cancer cells,and AFP also antagonism this effect of ATRA.The results of the laser confocal microscopy shown that co-location of AFP and RAR-α/γin the cells of liver cancer cells.The results of the Western Blot shown that HLE,Bel7402,and PLC expressed AFP,RAR-α/γ,Survivin,Bcl-2 are expressed in.The expression of AFP was inhibited while PLC cells were transfected with si RNA-AFP923,and the expression was stimulated in HLE cells while transfected with pc DNA3.1-EGFP-afp vectors.Conclusions: ATRA was able to inhibite the growth of HCC cells;AFP could induce the resistance of HCC cells on the effect of ATRA,the role mechanism of AFP maybe involve in interaction of AFP with RAR-α/γ in HCC cells.