AIM: To study the effects of QHF-cisplatin on H22 hepatocellular carcinoma(HCC) and their mechanisms of action.METHODS: Sixty BALB/c mice were randomly divided into a model group(n = 48) and a normal control group(n =...AIM: To study the effects of QHF-cisplatin on H22 hepatocellular carcinoma(HCC) and their mechanisms of action.METHODS: Sixty BALB/c mice were randomly divided into a model group(n = 48) and a normal control group(n = 12). An HCC xenograft tumor was created by injecting H22 cells directly into the liver parenchyma of the mice. The 48 BALB/c mice in the model group were randomly divided into four groups: QHF, DDP(cisplatin), QHF plus DDP, and model control. The inhibitory effects of these drugs on tumor growth were evaluated by calculating the rate of tumor growth inhibition. The mice were examined by observing their general condition, body weight and survival time. Changes in tumor tissue were observed under anoptical microscope. Aspartate aminotransferase(AST), alanine aminotransferase(ALT) and α-fetoprotein(AFP) levels in serum were measured. Hepatocyte growth factor(HGF), c-mesenchymal-epithelial transition(c-Met) factor, phosphorylated(p)-c-Met, p38, p-p38, extracellular signal-regulated kinase(ERK), p-ERK and vascular endothelial growth factor(VEGF) levels were evaluated in tumor and liver tissues using western blotting. RESULTS: Compared with the DDP group, a lower incidence of toxic reactions and a higher survival time were observed in the QHF plus DDP group. Tumor weight was significantly lower in the QHF, DDP and QHF plus DDP groups than in the model control group(0.24 ± 0.07, 0.18 ± 0.03 and 0.14 ± 0.01 g vs 0.38 ± 0.05 g, respectively), and the differences were statistically significant(P < 0.01). The rate of tumor growth inhibition in the QHF, DDP and QHF plus DDP groups was 38.7%, 52.6% and 63.5%, respectively. AST, ALT and AFP levels in serum were significantly lower in the QHF, DDP and QHF plus DDP groups compared to the model control group(P < 0.05). Similarly, HGF, p-c-Met, p-p38, p-ERK and VEGF levels in tumor tissue were significantly lower in the QHF, DDP and QHF plus DDP groups(P < 0.05).CONCLUSION: QHF and DDP have an antiangiogenic effect on H22 HCC in mice. QHF inhibits tumor growth via blocking the HGF/c-Met signaling pathway, inhibiting p38, ERK and VEGF signaling.展开更多
目的探讨分子佐剂修饰的VEGF融合蛋白疫苗与低剂量环磷酰胺(CTX)能否产生协同抗肝癌作用。方法建立小鼠H22肝癌模型,将BALB/c小鼠随机分为4组:生理盐水对照组、CTX单药组、VEGF蛋白疫苗单药组(V2组)、V2与CTX联合治疗组(V2+CTX)。分别在...目的探讨分子佐剂修饰的VEGF融合蛋白疫苗与低剂量环磷酰胺(CTX)能否产生协同抗肝癌作用。方法建立小鼠H22肝癌模型,将BALB/c小鼠随机分为4组:生理盐水对照组、CTX单药组、VEGF蛋白疫苗单药组(V2组)、V2与CTX联合治疗组(V2+CTX)。分别在H22肝癌皮下移植瘤及皮内肿瘤模型中评价联合治疗方案抗肿瘤生长及抗血管生成的能力,并通过Western blot及ELISA方法检测抗-VEGF抗体水平。结果皮下移植瘤模型结果显示V2+CTX联合治疗组的肿瘤体积、平均瘤重低于各单药治疗组(P<0.05 vs V2,P<0.01 vs CTX);在皮内肿瘤血管模型中,联合治疗对肿瘤新生血管的抑制作用最为明显,与单独的V2及CTX组相比,差异均有统计学意义(P<0.05 vs V2,P<0.01 vs CTX);Western blot及ELISA的结果显示,V2+CTX联合治疗诱导小鼠产生了高水平的特异性抗-VEGF抗体。结论低剂量CTX与重组VEGF融合蛋白疫苗联合治疗有协同抗肝癌作用。展开更多
基金Supported by Grants from the Natural Science Foundation of Hubei Province,China,No.2011CAD039
文摘AIM: To study the effects of QHF-cisplatin on H22 hepatocellular carcinoma(HCC) and their mechanisms of action.METHODS: Sixty BALB/c mice were randomly divided into a model group(n = 48) and a normal control group(n = 12). An HCC xenograft tumor was created by injecting H22 cells directly into the liver parenchyma of the mice. The 48 BALB/c mice in the model group were randomly divided into four groups: QHF, DDP(cisplatin), QHF plus DDP, and model control. The inhibitory effects of these drugs on tumor growth were evaluated by calculating the rate of tumor growth inhibition. The mice were examined by observing their general condition, body weight and survival time. Changes in tumor tissue were observed under anoptical microscope. Aspartate aminotransferase(AST), alanine aminotransferase(ALT) and α-fetoprotein(AFP) levels in serum were measured. Hepatocyte growth factor(HGF), c-mesenchymal-epithelial transition(c-Met) factor, phosphorylated(p)-c-Met, p38, p-p38, extracellular signal-regulated kinase(ERK), p-ERK and vascular endothelial growth factor(VEGF) levels were evaluated in tumor and liver tissues using western blotting. RESULTS: Compared with the DDP group, a lower incidence of toxic reactions and a higher survival time were observed in the QHF plus DDP group. Tumor weight was significantly lower in the QHF, DDP and QHF plus DDP groups than in the model control group(0.24 ± 0.07, 0.18 ± 0.03 and 0.14 ± 0.01 g vs 0.38 ± 0.05 g, respectively), and the differences were statistically significant(P < 0.01). The rate of tumor growth inhibition in the QHF, DDP and QHF plus DDP groups was 38.7%, 52.6% and 63.5%, respectively. AST, ALT and AFP levels in serum were significantly lower in the QHF, DDP and QHF plus DDP groups compared to the model control group(P < 0.05). Similarly, HGF, p-c-Met, p-p38, p-ERK and VEGF levels in tumor tissue were significantly lower in the QHF, DDP and QHF plus DDP groups(P < 0.05).CONCLUSION: QHF and DDP have an antiangiogenic effect on H22 HCC in mice. QHF inhibits tumor growth via blocking the HGF/c-Met signaling pathway, inhibiting p38, ERK and VEGF signaling.
文摘目的探讨分子佐剂修饰的VEGF融合蛋白疫苗与低剂量环磷酰胺(CTX)能否产生协同抗肝癌作用。方法建立小鼠H22肝癌模型,将BALB/c小鼠随机分为4组:生理盐水对照组、CTX单药组、VEGF蛋白疫苗单药组(V2组)、V2与CTX联合治疗组(V2+CTX)。分别在H22肝癌皮下移植瘤及皮内肿瘤模型中评价联合治疗方案抗肿瘤生长及抗血管生成的能力,并通过Western blot及ELISA方法检测抗-VEGF抗体水平。结果皮下移植瘤模型结果显示V2+CTX联合治疗组的肿瘤体积、平均瘤重低于各单药治疗组(P<0.05 vs V2,P<0.01 vs CTX);在皮内肿瘤血管模型中,联合治疗对肿瘤新生血管的抑制作用最为明显,与单独的V2及CTX组相比,差异均有统计学意义(P<0.05 vs V2,P<0.01 vs CTX);Western blot及ELISA的结果显示,V2+CTX联合治疗诱导小鼠产生了高水平的特异性抗-VEGF抗体。结论低剂量CTX与重组VEGF融合蛋白疫苗联合治疗有协同抗肝癌作用。
