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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细胞增殖和裸鼠移植瘤生长具有显著抑制作用,同时具有抗肿瘤血管生成效应。
OBJECTIVE: To study the inhibitory effect of recombinant vascular basement membrane-derived multifunctional peptide rVBMDMP on the growth and angiogenesis of human hepatoma HepG2 xenografts in nude mice. Methods: Human hepatocellular carcinoma HepG2 cells and human embryonic liver L-02 cells were cultured in vitro. MTT assay was used to determine the inhibitory effect of rVBMDMP on HepG2 cells. MTT assay was used to evaluate the inhibitory effect of rVBMDMP on HepG2 cells. The proportion of microvessel area (MVA) in the xenografts of nude mice bearing rVBMDMP was analyzed by CD31 immunohistochemistry. Results: rVBMDMP selectively inhibited the proliferation of HepG2 cells in vitro in a dose-dependent manner, but had no effect on the proliferation of L-02 cells. rVBMDMP significantly inhibited the growth of HepG2 xenografts in a dose-dependent manner. The tumor growth inhibition rates of rVBMDMP at 1.0 mg / kg, 3.0 mg / kg and 10.0 mg / kg were 12.4%, 55.8% and 79.7%, respectively. The tumor growth inhibition rate of 10.0 mg / kg rVBMDMP was similar to that of 20-mg / kg 5-fluorouracil (5-FU, 80.1%). The percentage of CD31 positive area of rVBMDMP-treated human hepatoma HepG2 xenografts in nude mice significantly decreased with the increase of rVBMDMP concentration. Conclusion: rVBMDMP can significantly inhibit the proliferation of human hepatocellular carcinoma HepG2 cells and the growth of transplanted xenografts in nude mice, and has anti-angiogenic effect.