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目的:观察重组血管基膜衍生多功能肽(Vascular basement membrane derived multifunctional peptide,VBM-DMP)对人肺癌细胞增殖的选择性抑制作用。方法:体外培养人肺癌(A549)细胞、人胚肺二倍体成纤维细胞(KMB-17),采用MTT比色法测定重组VBMDMP对A549细胞增殖的选择性抑制作用;台盼蓝染色细胞计数法观察重组VBMDMP对A549细胞和KMB-17细胞生长曲线的影响;采用人肺癌(A549)细胞裸鼠异种移植瘤模型治疗实验,评价重组VBMDMP治疗人肺癌的有效性。结果:体外实验结果表明重组VBMDMP能选择性抑制人肺癌(A549)细胞的增殖和生长,呈剂量依赖性,而对KMB-17细胞的增殖活性影响小;重组VBMDMP显著抑制人肺癌(A549)细胞裸鼠异种移植瘤的生长,呈剂量依赖性趋势。1 mg/kg和5 mg/kg重组VBMDMP的肿瘤生长抑制率分别是42%和74%,瘤重抑制率分别42%和77%,其中5mg/kg重组VBMDMP的肿瘤生长抑制率和瘤重抑制率均高于环磷酰胺(CTX100 mg/kg)、血管生成抑制剂烟曲霉素衍生物TNP-470(20 mg/kg)。结论:重组VBMDMP对人肺癌细胞(A549)的增殖和生长具有显著抑制作用,是一种选择性高,抗肿瘤作用强的新型抗肿瘤基因工程候选药物。
Objective: To observe the selective inhibition of proliferation of human lung cancer cells by recombinant vascular derived membrane-derived multifunctional peptide (VBM-DMP). Methods: Human lung cancer A549 cells and human embryonic lung diploid fibroblasts (KMB-17) were cultured in vitro. The selective inhibition of recombinant human VBMDMP on the proliferation of A549 cells was determined by MTT assay. The expression of trypan blue staining Method to observe the effect of recombinant VBMDMP on the growth curve of A549 cells and KMB-17 cells. The human lung cancer A549 cell xenograft model was used to treat the experiment, and the effectiveness of recombinant VBMDMP in the treatment of human lung cancer was evaluated. Results: The results of in vitro experiments showed that VBMDMP could selectively inhibit the proliferation and growth of human lung cancer A549 cells in a dose-dependent manner, but had little effect on the proliferation of KMB-17 cells. Recombinant VBMDMP significantly inhibited the proliferation of human lung cancer A549 cells Growth of nude mice xenografts in a dose-dependent manner. The tumor growth inhibition rates of 1 and 5 mg / kg recombinant VBMDMP were 42% and 74%, respectively, and the tumor weight inhibition rates were 42% and 77% respectively. The tumor growth inhibition rate and tumor weight inhibition of 5 mg / kg recombinant VBMDMP Rates were higher than cyclophosphamide (CTX 100 mg / kg), the angiogenesis inhibitor fumagillin derivative TNP-470 (20 mg / kg). Conclusion: Recombinant VBMDMP can significantly inhibit the proliferation and growth of human lung cancer cells (A549), and is a new anti-tumor gene engineering candidate with high selectivity and anti-tumor effect.