重组血管基膜衍生多功能肽抑制人肝癌HepG2裸鼠移植瘤生长和血管生成

目的:研究重组血管基膜衍生多功能肽rVBMDMP对人肝癌HepG2裸鼠移植瘤生长和血管生成的抑制作用。方法:体外培养人肝癌HepG2细胞和人胚肝L-02细胞,MTT法测定不同浓度的rVBMDMP对HepG2细胞的选择性抑制增殖作用;人肝癌HepG2裸鼠移植瘤模型治疗实验评价rVBMDMP体内抗人肝癌作用;CD31免疫组化方法分析rVBMDMP处理的HepG2裸鼠移植瘤组织微血管面积(MVA)的比例。结果:rVBMDMP具有选择性抑制体外培养人肝癌HepG2细胞增殖作用,呈剂量依赖性,而对L-02细胞的增殖活性无明显的影响。rVBMDMP对HepG2裸鼠移植瘤生长具有显著抑制作用,呈剂量依赖性。1.0 mg/kg、3.0 mg/kg和10.0 mg/kg的rVBMDMP的肿瘤生长抑制率分别为:12.4%,55.8%和79.7%。其中10.0 mg/kg的rVBMDMP的肿瘤生长抑制率近似于20.0 mg/kg的5-氟尿嘧啶(5-FU,80.1%)。rVBMDMP处理的人肝癌HepG2裸鼠移植瘤组织的CD31染色阳性区域面积百分比随着rVBMDMP浓度的增加明显降低。结论:rVBMDMP对人肝癌HepG2细胞增殖...

Vascular Basement Membrane-derived Multifunctional Peptide Inhibits Angiogenesis and Tumor Growth of Hepatocellular Carcinoma HepG2 Xenograft in nude mice

Objective To explore the Inhibition of angiogenesis and tumor growth in human hepatocellular carcinoma HepG2 xenograft mouse model by a recombinant vascular basement membrane-derived multifunctional peptide(rVBMDMP).Methods HepG2 and Human Embryo Liver(L-02) cells were incubated in vitro;Different concentration rVBMDMP selectively inhibited the proliferation of HepG2 cells was examined by MTT assay.Therapeutic trial of human hepatocellular carcinoma xenograft in nude mice was used to evaluate the anti-tumor activity of rVBMDMP in vivo.Immunohistochemistry for CD31 was assessed the rate of the microvessel area(MVA) of tumor tissue treated with rVBMDMP.Results rVBMDMP could selectively inhibit the proliferation of HepG2 cells,in a dose-dependent manner,with little effect on L-02 cells.The therapeutic trial for human hepatocellular carcinoma xenograft in nude mice by rVBMDMP suggested that rVBMDMP possessed significant inhibitory growth effect of human hepatocellular carcinoma xenograft in a dose-dependent manner.The inhibitory rate of xenograft growth was 12.4%,55.8% and 79.7% treated with rVBMDMP at 1.0 mg/kg,3.0 mg/kg and 10.0 mg/kg,respectively.The inhibitory effect of xenograft growth with rVBMDMP at 10.0 mg/kg was nearly close to 5-Fluorouracil(5-FU,80.1%) at 20.0 mg/kg.Immunohistochemistry analysis displayed that the ratio of MVA was reduced along with increasing of the concentration of rVBMDMP.Conclusion rVBMDMP could markedly inhibit the proliferation of human hepatocellular carcinoma cells and growth of tumor xenograft as well as suppress angiogenesis in nude mice.