| Obejective:To evaluate the suppression of HCC cells and vascular endothelial with Gensenoside Rg3. Materials and methods:Rat HCC cell lines (McA-RH7777) and human umbilical vein endothelial cell (HUVEC) were used in this part. The proliferation or toxicity of VEGF-165, PDGF-BB and Gensenoside Rg3for these cells was detected by WST-1method. The apoptosis of these cells with Gensenoside Rg3was also detected with PI staining method by flow cytometry. The inhibition of HUVEC with Gensenoside Rg3was tested by cell scratch test. The inhibition of VEGFR-2、p VEGFR-2、PDGFR-β and p PDGFR-β with Gensenoside Rg3in different concentration was detected by cell immunofluorescence and western blotting (WB). All data were processed by SPSS11.0. Results:The proliferation of HUVEC was promoted by VEGF at10ng/mL and above, or by PDGF at10ng/mL and above (P<0.05). The proliferation of HCC cell (McA-RH7777) was promoted by VEGF+PDGF at25ng/ml and above(P<0.05). The proliferation of HUVEC and McA-RH7777cells was suppressed by Gensenoside Rg3signigicantly at0.001μM and above(P<0.001). The apoptosis of HUVEC was4.05%without Gensenoside Rg3,12.56%at0.1μM of Gensenoside Rg3and20.06%at1μM Gensenoside Rg3by flow cytometry.While, the apoptosis of McA-RH7777cells was2.74%,10.22%,17.53%with OμM,0.1μM,1μM Gensenoside Rg3. HUVEC didn’t cross the scratch after incubation with Gensenoside Rg3in Scratch test. The phosphorylation of VEGFR-2of HUVEC and McA-RH7777cells was suppressed by Gensenoside Rg3in cell immunofluorescence test. The phosphorylation of VEGFR-2and PDGFR-β was found to be suppressed by Gensenoside Rg3in Western blotting test, but not in expression of VEGFR-2and PDGFR-β. Conclusions:1. Gensenoside Rg3can suppress the proliferation of HUVEC and promotes its apoptosis.2. Gensenoside Rg3can also inhibite HCC cells at high concentration. Obejective:To investigate the effects of the combination of TAE and Gensenoside Rg3for HCC in rat model, and study the mechanism of angiogenesis and molecular level. Materials and methods:Rat HCC models, established with McA-RH7777and Buffalo strait rats, were divided randomly into four groups:saline group (group A, control group), Rg3group (group B), TAE group (group C), TAE+Rg3group (group D). Rat survival time, tumor diameter, weight and tumor metastasis were evaluated. MRI plain scan were applied for five groups at1week,2weeks,4weeks and8weeks after surgery and at the same time, some rats were sacrificed for the detection of MVD(labeled by CD31), HIF-la, VEGF, VEGFR-2, p VEGFR-2and b-FGF with IHC and/or WB. All data were processed by SPSS11.0. Results:There was statistical difference in survival time among4groups (P<0.05), and group B and group D had longer survival than group A between each two groups compare (P<0.05). The hazard ratio in group D compared to group C was0.32,95%CI (0.034-3.111),(P=0.328), while group B compared to group A was0.11,95%CI (0.013-0.954),(P=0.045)。The diameter of tumor increased significantly faster than other three group(P<0.05). The occurrences of metastasis in group B and group D which Rg3was used were significantly lower than those in group A and group C(P<0.05). The weight of rats in group B and D was significantly superior to that in group A and C (P <0.05). VEGF expression of tumor was significantly different among4groups2weeks later after intervention by ELISA test (P<0.001), which was significantly lower in group B and D (P<0.05). MVD of tumor was significantly different among4groups all time after intervention by IHC (P<0.05), which was significantly lower in group B and group D (P<0.05). HIF-1α expression of tumor was not significantly different (P>0.05) except which was higher in group C and D compared with group A and B at1week after intervention by IHC (P<0.05). VEGF expression of tumor in group D was significantly lower than that in group C by IHC (P<0.05). VEGFR-2expression in group B and D was significantly lower than that in group A and C4weeks later after intervention by IHC (P<0.05). Expression of p-VEGFR-2was significantly lower in group B than it in group A at first two weeks after intervention by IHC (P<0.05), but it was until4weeks later after TAE that p-VEGFR-2in group D was lower than it in group C (P<0.05). WB test showed that CD31in group D was lower than it in group C at2and4weeks (P<0.05), while it in group B was lower than it in group A all time after intervention (P<0.05). Expression of b-FGF in group B and D was lower than it in group A and D all time by WB test (P<0.05). However, the expression and phosphorylation of VEGFR-2was inhibited significantly among4groups all time after intervention (P<0.05). Conclusions:Gensenoside Rg3, with combination of TAE for treatment of HCC, inhibits several angiogenesis-related receptors, suppresses angiogenesis, and enhances the effect of TAE. Obejective:To investigate the effects and safety of the combination of TACE and Gensenoside Rg3for HCC in patients, and study the mechanism of angiogenesis and molecular level. Materials and methods:Two haundren and eighty two patients were divided into two groups:TACE+Rg3group (n=141) and TACE group (n=141). All patients received TACE as regular and patients in TACE+Rg3group took Gensenoside Rg340mg/d at least3months. Primary outcomes were overall survival and Progression free survival. Secondary outcomes included the response rate, metastasis rate, serum VEGF level, and and safety. Results:At the end of study,80patients in TACE+Rg3group and82patients in TACE group were under analysis. And62deaths had occurred,29in TACE+Rg3group and33in TACE group. Median overall survivial was no difference in two groups(24months vs24months, P=0.092), but in all Child B patients, median survival was25months (95%CI13.2-36.8) in TACE+Rg3group vs14months in TACE group (95%CI10.7-17.3), P=0.023。 HR=0.33,95%CI(0.12-0.91), P=0.033。Median PFS was also no difference5months in TACE+Rg3group and4months in TACE group (P=0.064), HR=0.75,95%CI (0.54-1.04), P=0.089。But in all Child B patients, median PFS was5months (95%CI3.8-6.2months) in TACE+Rg3group vs3months,(95%CI1.9-4.0months) in TACE group, P=0.005。HR=0.46,95%CI (0.24-0.85), P=0.014. Response rate (PR+SD) in TACE+Rg3group was significantly better than it in TACE group (72.5%vs56.1%, P=0.029). There was less lymph nodes metastasis found in TACE+Rg3group (27.5%vs43.9%, P=0.029). The levels of serum VEGF in TACE+Rg3group was significantly lower than those in TACE group after2months and6months therapy (P=0.000). The recovery of white blood cell level,serum total bilirubin level and weight was better in TACE+Rg3group (P<0.05). There was no difference in other adverse events. Conclusion:Gensenoside Rg3is effective and safe with TACE to control HCC, and it can suppress VEGF protein expression. |
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