The Significance Of Expression Of Platelet-derived Growth Factor-D And It's Receptor In Hepatocellular Carcinoma

Objective: To investigate the significance of expressions of platelet - derived growth factor (PDGF)-D and it's receptor PDGFRβgene in hepatocellular carcinoma (HCC) tissues , and the influence of exogenous PDGF-D on the proliferation of human liver tummor cell and expression of vascular endothelial growth factor (VEGF) , matrix metalloproteinases (MMP)-9 gene and protein in human liver tummor cell strain BEL-7402.Methods: PDGF-D and PDGFRβmRNA expression were assessed by reverse transcription-polymerase chain reaction (RT-PCR) in 40 cases HCC tissues , 30 cases of paracarcinoma tissues , 10 cases of normal liver tissues,human liver tummor cell strain BEL-7402 and paracarcinoma cell strain QSG-7701 . BEL-7402 were treated with different concentration (0 , 5 , 10 , 20 , 50 , 100pg/ml) of exogenous PDGF-DD. Cell proliferation was measured using the MTT assay.The effect of exogenous PDGF-DD on cell cycle of BEL-7402 cells was assessed by flow cytometry . The expression of VEGF and MMP-9 were detected by RT-PCR and ELISA in BEL-7402 cells which were exposed to different concentration of PDGF-DD.Results: PDGF-D and PDGFRβmRNA expression were 92.5% (37/40) ,26.7% (8/30) , 42.5% (17/40) , 16.7% (5/30) in HCC and paracarcinoma tissues respectively . No expression of PDGF-D mRNA was found in the normal liver tissues . PDGF-D and PDGFRβmRNA expression was significantly higher than in paracarcinoma tissues and normal liver tissues , there were significantly differences between the three groups (P<0.01) . PDGF-D mRNA expression were related to tumor differentiation degree and metastasis , but not to gender , age , tumor size and portal vein cancer embolus (P> 0.05). PDGF-D and PDGFRβmRNA expression in human liver tummor cell strain BEL-7402 was significantly higher than those in paracarcinoma cell strain QSG-7701(P<0.05). Exogenous PDGF-DD promoted proliferation of tumor cells compared with the control group in a dose-dependent manner from 10pg/ml to 100pg/ml (P<0.05) . The effect of PDGF-DD in 100pg/ml was more powerful than in other concentrations . Incubation of tumor cells with PDGF-DD markedly decreased the cell percentage of the G0/G1 -phase and increased that of the S-phase . Compared with control group (0 pg/ml) , VEGF , MMP-9 and PDGFRβmRNA expressions in experimental groups (PDGF-DD from 10pg/ml to 200pg/ml) were increased (P<0.05). However,for VEGF mRNA expression , there was no significant difference between 50pg/ml group and 100pg/ml group , Also , for MMP-9 and PDGFRβmRNA expression , no significant difference was noted between 5pg/ml group and 10pg/ml group.VEGF protein protein expressions in experimental groups were significantly enhanced by exogenous PDGF - DD in a dose - dependent manner,except 5pg/ml groups . Similarly , VEGF protein protein expressions in experimental groups were significantly higher than those in control group (0 pg/ml) . However , there was no significant difference between 5pg/ml group and 100pg/ml group , and between 10pg/ml and 20pg/ml .Conclusion: PDGF-D may play an important role in the carcinogenesis , development and metastasis of HCC . It might be as a prognostic factor and a potential target for therapy in HCC.