Effects of combination anti-vascular endothelial growth factor receptor and anti-epidermal growth factor receptor therapies on the growth of gastric cancer in a nude mouse model
Effects of combination anti-vascular endothelial growth factor receptor and anti-epidermal growth factor receptor therapies on the growth of gastric cancer in a nude mouse model
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DOI：
10.1016/s0959-8049(02)00013-8
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发表时间：
2002-05-01
影响因子：
8.4
通讯作者：
Ellis, LM
中科院分区：
文献类型：
--
作者：
Jung, YD;Mansfield, PF;Ellis, LM
我们假设抗血管生成和抗表皮生长因子（EFG）受体（R）联合治疗比单药治疗更有效地抑制胃癌生长。将TMK-1胃癌细胞注射到裸鼠的胃壁中以产生肿瘤。4天后，将小鼠随机分配到以下组：对照组、DC 101（[血管内皮生长因子（VEGF）-受体（R）-2抗体]）、C225（EGF-R抗体）或DC 101和C225的组合。与对照组相比，联合治疗显著抑制了胃肿瘤生长，而单独用DC 101或C225治疗的小鼠中肿瘤生长的减少没有达到统计学显著性。所有给予DC 101的小鼠均表现出肿瘤血管分布减少和内皮细胞凋亡增加。C225单独不影响血管生成，但抑制肿瘤细胞增殖。联合治疗导致肿瘤细胞增殖进一步减少。抗VEGF-R和抗EGF-R的联合治疗对抑制胃癌生长是有效的。这些发现支持了抑制介导肿瘤生长的多种生物学途径可能是一种有效的治疗策略的假设。(C)2002年由Elsevier Science Ltd.出版
We hypothesised that the combination of anti-angiogenic and anti-epidermal growth factor (EFG)-receptor (R) therapies would more effectively inhibit gastric cancer growth than single-agent therapy. TMK-1 gastric cancer cells were injected into the gastric wall of nude mice to generate tumours. After 4 days, mice were randomly assigned to the following groups: control, DC101 ([vascular endothelial growth factor (VEGF)-receptor (R)-2 antibody], C225 (EGF-R antibody), or a combination of DC 10 1 and C225. The combination therapy significantly inhibited gastric tumour growth compared with the control group, whereas the decrease in tumour growth in mice treated with DC101 or C225 alone did not reach statistical significance. All mice administered DC101 demonstrated decreased tumour vascularity and increased endothelial cell apoptosis. C225 alone did not affect angiogenesis, but inhibited tumour cell proliferation. The combination therapy led to a further decrease in tumour cell proliferation. The combination of anti-VEGF-R and anti-EGF-R therapies was effective in inhibiting gastric cancer growth. These findings support the hypothesis that inhibiting multiple biological pathways that mediate tumour growth may be an effective therapeutic strategy. (C) 2002 Published by Elsevier Science Ltd.