Chemoresistance of hepatocellular carcinoma to interferon α therapy and possible mechanism

ObjectiveTo investigate the chemoresistance of hepatocellular carcinoma (HCC) to interferonα(IFN-α) treatment and to explore the possible mechanism.MethodsNude mice with LCI- D20 were randomized into 4 treatment groups A-D and control groups E-G (n=6 each group).IFN-αwas administrated subcutaneously at dosages of 1.5×10~7 U/(kg.d) for 20 days,then the nude mice in groups A and B were sacrificed at day 28 and 48 respectively;The nude mice in groups C and D received IFN-α(1 5 x 10~7 U/kg.d) and Glivec (100 mg/kg,d,p.o.) combined with IFN-α(1.5×10~7 U/kg.d) treatment again at day 48 respectively for 20 days;The nude mice in groups E,F and G were sacrificed at day 28,48,68 respectively.Tumor size and diameter,microvessel density and serum VEGF concentration were recorded.SuperArray eDNA chips about angiogenesis of groups A,D,E and G were used.Results The tumor weight of groups A-G was 0.27,1.54,3.22,2.23,0.68,1.93 and 3.98 g respectively,and there was statistically significant difference between groups A and E,groups D and G (P＜0.05).The serum VEGF concentration of group A and groups C,D was lower than that of group E and group G re- spectively.The results of eDNA array revealed that during IFN-αtreatment process EVGF gene expres- sion maintained low level,whereas PDGF-A gene expression held high level.The microvessel density of group A was lower than that of group E statistically.HE staining showed tumor from IFN-αtreatment had a more invasive and malignant phenotype.ConclusionChemoresistance of HCC emerges to IFN-αtherapy and this resistance involves vascular regrowth in a PDGF-A independent second wave of anglo- genesis.