AMD3100对胰腺癌细胞AsPC-1及其移植瘤血管生成的影响

Effect of AMD3100 on the proliferation and angiogenesis of AsPC-1 cells

目的探讨非肽类特异性CXCR4拮抗剂AMD3100对胰腺癌细胞株AsPC-1细胞增殖及其移植瘤生长的影响。方法AsPC-1细胞分为对照组、基质细胞衍生因子-1（SDF-1α）处理组、AMD3100处理组和SDF-1α＋AMD3100处理组，MTT法检测细胞增殖，Westernblotting检测血管内皮生长因子（VEGF）表达。建立AsPC-1细胞裸鼠移植瘤模型，应用AMD3100瘤内及瘤周注射，观察移植瘤的生长，免疫组化法检测裸鼠移植瘤的微血管密度（microvesseldensity，MVD）。结果SDF-1a可明显促进AsPC-1细胞增殖（1．430±0．122对1．002±0．001，P〈0．05），而同时应用AMD3100处理能抑制这种增殖反应（0．983±0．068对1．430±0．122，P〈0．05）；SDF-1仅亦可促进AsPC-1细胞VEGF的表达（0．565±0．047对0．439±0．034，P〈0．05），而同时用AMD3100处理可抑制这种效应（0．450±0．071对0．565±0．047，P〈0．05）。AMD3100可抑制AsPC-1细胞皮下移植瘤的生长，第24天的抑瘤率达59．5％，移植瘤的MVD显著减少（28．56±6．94对98．75±20．60，P〈0．01）。结论AMD3100在体外和体内均可抑制AsPC-1细胞增殖及其移植瘤的血管生成。

Objective To investigate the effects of blockade on non-peptide specific SDF-1/CXCR4 receptor ligand system with AMD3100 on the proliferation and angiogenesis of human pancreatic cancer cells AsPC-1. Methods AsPC-1 was divided into control group, SDF-1α group, group, SDF-1α ＋ AMD3100 group. MTT test was performed to determine the proliferative level of AsPC-1 cells. Vascular endothelial growth factor （VEGF） was detected with Western blotting assay. Immunohistochemistry was used to detect the microvessel density （MVD） in subcutaneous xenografts of AsPC 1 of nude mice model, which was intratumorally and peritumorally injected with AMD3100. Results SDF-1α could induce the proliferation of AsPC-1（1.430 ±0. 122 vs 1. 002 ± 0. 001, P 〈0.05）. While the proliferative effect induced by SDF-1α could be inhibited by AMD3100 （0. 983 ±0.068vs 1.430 ± 0. 122, P 〈0.05）. SDF-1α could induce the expression of VEGF （0. 565±0.047 vs 0. 439 ± 0.034, P 〈0. 05）. While the protein expression of VEGF induced by SDF-1α on AsPC-1 cells was inhibited by AMD3100 （0. 450 ±0. 071 vs 0. 565 ± 0.04, P 〈 0.05 ）. The growth and angiogenesis of subcutaneous xenografts of nude mice model were inhibited by AMD3100; the tumor inhibitory rate was 59. 5% at 24th day. The MVD of xenografts was significantly decreased （28. 56 ±6. 94 vs 98. 75 ±20. 60, P 〈 0. 01 ）. Conclusions AMD3100 could inhibit the proliferation and angiogenesis of AsPC-1 cells both in vitro and in vivo.