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AIM:Transcatheter arterial embolization (TAE) of the hepaticartery has been accepted as an effective treatment forunresectable hepatocellular carcinoma (HCC).However,embolized vessel recanalization and collateral circulationformation are the main factors of HCC growth and recurrenceand metastasis after TAE.Vascular endothelial growth factor(VEGF) plays an important role in tumor angiogenesis.Thisstudy was to explore the inhibitory effect of VEGF antisenseoligodeoxynucleotides (ODNs) on VEGF expression incultured Walker-256 cells and to observe the anti-tumoreffect of intra-arterial infusion of antisense ODNs mixed withlipiodol on rat liver cancer.METHODS:VEGF antisense ODNs and sense ODNs wereadded to the media of non-serum cultured Walker-256 cells.Forty-eight hours later,VEGF concentrations of supernatantswere detected by ELISA.Endothelial cell line ECV-304 cellswere cultured in the supernatants.Seventy-two hours later,growth of ECV-304 cells was analyzed by MTT method.ThirtyWalker-256 cell implanted rat liver tumor models were dividedinto 3 groups.0.2 mL lipiodol (LP group,n=10),3OD antisenseODNs mixed with 0.2 mL lipiodol (LP+ODNs group,n=10)and 0.2 mL normal saline (control group,n=10) were infusedinto the hepatic artery.Volumes of tumors were measuredby MRI before and 7 d after the treatment.VEGF mRNA incancerous and peri-cancerous tissues was detected by RT-PCR.Microvessel density (MVD) and VEGF expression wereobserved by immunohistochemistry.RESULTS:Antisense ODNs inhibited Walker-256 cells’VEGF expression.The tumor growth rate was significantlylower in LP+ODNs group than that in LP and control groups(140.1±33.8%,177.9±64.9% and 403.9±69.4%respectively,F=60.019,P<0.01).VEGF mRNAs in cancerousand peri-cancerous tissues were expressed highest in LPgroup and lowest in LP+ODNs group.The VEGF positive ratesshowed no significant difference among LP,control andLP+ODNs groups (90%,70% and 50%,H=3.731,P>0.05).The MVD in LP+ODNs group (53.1±18.4) was significantlyless than that in control group (73.2±20.4) and LP group(80.3±18.5) (F=5.44,P<0.05).CONCLUSION:VEGF antisense ODNs can inhibit VEGF expression of Walker-256 cells.It may be anantiangiogenesis therapy agent for malignant tumors.VEGFantisense ODNs mixed with lipiodol embolizing liver canceris better in inhibiting liver cancer growth,VEGF expressionand microvessel density than lipiodol alone.
AIM: Transcatheter arterial embolization (TAE) of the hepaticartery has been accepted as an effective treatment forunresectable hepatocellular carcinoma (HCC) .However, embolized vessel recanalization and collateral circulationformation are the main factors of HCC growth and recurrenceand metastasis after TAE. Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. This study was to explore the inhibitory effect of VEGF antisense oligodeoxynucleotides (ODNs) on VEGF expression in cultured Walker-256 cells and observe the anti-tumoreffect of intra-arterial infusion of antisense ODNs mixed with lipiodol on rat liver cancer. METHODS: VEGF antisense ODNs and sense ODNs wereadded to the media of non-serum cultured Walker-256 cells. Forty-eight hours later, VEGF concentrations of supernatantswere detected by ELISA. Endothelial cell line ECV-304 cellswere cultured in the supernatants. Seventy-two hours later, growth of ECV-304 cells were analyzed by MTT method. dirty Walker-2 56 cell implanted rat liver tumor models were dividedinto 3 groups with 0.2 mL lipiodol (LP group, n = 10), 3 OD antisense ODNs mixed with 0.2 mL lipiodol (LP + ODNs group, n = 10) and 0.2 mL normal saline Volumes of tumors were measured by MRI before and after 7 d after the treatment. VEGF mRNA was detected by RT-PCR. Microvessel density (MVD) and VEGF expression wereobserved by immunohistochemistry .RESULTS: Antisense ODNs inhibited Walker-256 cells’VEGF expression. The tumor growth rate was significantly lower in LP + ODNs group than that in LP and control groups (140.1 ± 33.8%, 177.9 ± 64.9% and 403.9 ± 69.4% respectively, F = 60.019, P <0.01) .VEGF mRNAs in cancerous and peri-cancerous tissues were highest in LPgroup and lowest in LP + ODNs group.The VEGF positive ratesshowed no significant difference among LP, control andLP + ODNs groups (90%, 70% and 50%, H = 3.731, P> 0.05) .The MVD in LP + ODNs group (53.1 ± 18.4) was significantly les(F = 5.44, P <0.05) .CONCLUSION: VEGF antisense ODNs can inhibit the VEGF expression of Walker-256 cells. It may be an antiangiogenesis therapy agent (73.2 ± 20.4) and LP group (80.3 ± 18.5) for malignant tumors. VEGF Antisense ODNs mixed with lipiodol embolizing liver canceris better in inhibiting liver cancer growth, VEGF expression and microvessel density than lipiodol alone.