Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors.
Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors.
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DOI：
10.1054/bjoc.2001.1936
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发表时间：
2001-08-17
影响因子：
8.8
通讯作者：
Ellis LM
中科院分区：
文献类型：
--
作者：
Shaheen RM;Ahmad SA;Liu W;Reinmuth N;Jung YD;Tseng WW;Drazan KE;Bucana CD;Hicklin DJ;Ellis LM
血管内皮生长因子（VEGF）和表皮生长因子（EGF）调节结肠癌的生长和转移。先前利用抗VEGF受体（DC101）或EGF受体（C225）的抗体的研究已经独立地证明，这些药物可以在体内和体外系统中抑制肿瘤生长并诱导结肠癌细胞凋亡。我们假设同时阻断VEGF和EGF受体将增强腹膜癌转移小鼠模型中结肠癌的治疗。给裸鼠腹膜内注射KM12L4人结肠癌细胞以产生腹膜转移。然后将小鼠随机分为四个治疗组之一：对照组、抗VEGFR（DC101）组、抗EGFR（C225）组或DC101和C225组。相对于对照组，用DC101或用DC101+C225处理减少了肿瘤血管分布、生长、增殖、腹水形成，并增加了肿瘤细胞和内皮细胞的凋亡。尽管C225治疗没有改变任何上述参数，但C225与DC101联合导致肿瘤血管分布显著减少，肿瘤细胞和内皮细胞凋亡增加（与DC101组相比）。这些发现表明，DC101抑制血管生成，内皮细胞存活，VEGF介导的腹水形成在结肠癌癌转移的小鼠模型。向DC101中添加C225似乎导致血管生成和腹水形成的进一步减少。联合抗VEGF和抗EGFR治疗可能代表一种新的治疗策略，用于结肠腹膜癌转移的管理。© 2001年癌症研究运动http://www.bjcancer.com
Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) regulate colon cancer growth and metastasis. Previous studies utilizing antibodies against the VEGF receptor (DC101) or EGF receptor (C225) have demonstrated independently that these agents can inhibit tumour growth and induce apoptosis in colon cancer in in vivo and in vitro systems. We hypothesized that simultaneous blockade of the VEGF and EGF receptors would enhance the therapy of colon cancer in a mouse model of peritoneal carcinomatosis. Nude mice were given intraperitoneal injection of KM12L4 human colon cancer cells to generate peritoneal metastases. Mice were then randomized into one of four treatment groups: control, anti-VEGFR (DC101), anti-EGFR (C225), or DC101 and C225. Relative to the control group, treatment with DC101 or with DC101+C225 decreased tumour vascularity, growth, proliferation, formation of ascites and increased apoptosis of both tumour cells and endothelial cells. Although C225 therapy did not change any of the above parameters, C225 combined with DC101 led to a significant decrease in tumour vascularity and increases in tumour cell and endothelial cell apoptosis (vs the DC101 group). These findings suggest that DC101 inhibits angiogenesis, endothelial cell survival, and VEGF-mediated ascites formation in a murine model of colon cancer carcinomatosis. The addition of C225 to DC101 appears to lead to a further decrease in angiogenesis and ascites formation. Combination anti-VEGF and anti-EGFR therapy may represent a novel therapeutic strategy for the management of colon peritoneal carcinomatosis. © 2001 Cancer Research Campaign http://www.bjcancer.com