针对血管内皮生长因子受体酪氨酸激酶受体的抗血管生成疗法可抑制结肠癌肝转移的生长，并诱导肿瘤和内皮细胞凋亡。

Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis.

作者信息

Shaheen R M, Davis D W, Liu W, Zebrowski B K, Wilson M R, Bucana C D, McConkey D J, McMahon G, Ellis L M

机构信息

Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

出版信息

Cancer Res. 1999 Nov 1;59(21):5412-6.

PMID:10554007

Abstract

Increased vascular endothelial growth factor (VEGF) expression is associated with colon cancer metastases. We hypothesized that inhibition of VEGF receptor activity could inhibit colon cancer liver metastases. BALB/c mice underwent splenic injection with CT-26 colon cancer cells to generate metastases. Mice received daily i.p. injections of vehicle, tyrosine kinase inhibitor for Flk-1/KDR (SU5416) or tyrosine kinase inhibitor for VEGF, basic fibroblast growth factor, and platelet-derived growth factor receptors (SU6668). SU5416 and SU6668 respectively inhibited metastases (48.1% and 55.3%), microvessel formation (42.0% and 36.2%), and cell proliferation (24.4% and 27.3%) and increased tumor cell (by 2.6- and 4.3-fold) and endothelial cell (by 18.6- and 81.4-fold) apoptosis (P<0.001). VEGF receptor inhibitors increased endothelial cell apoptosis, suggesting that VEGF may serve as an endothelial survival factor.

摘要

血管内皮生长因子（VEGF）表达增加与结肠癌转移相关。我们推测抑制VEGF受体活性可抑制结肠癌肝转移。BALB/c小鼠经脾脏注射CT-26结肠癌细胞以形成转移灶。小鼠每日腹腔注射溶剂、针对Flk-1/KDR的酪氨酸激酶抑制剂（SU5416）或针对VEGF、碱性成纤维细胞生长因子和血小板衍生生长因子受体的酪氨酸激酶抑制剂（SU6668）。SU5416和SU6668分别抑制转移（48.1%和55.3%）、微血管形成（42.0%和36.2%）以及细胞增殖（24.4%和27.3%），并增加肿瘤细胞凋亡（分别增加2.6倍和4.3倍）以及内皮细胞凋亡（分别增加18.6倍和81.4倍）（P<0.001）。VEGF受体抑制剂增加内皮细胞凋亡，提示VEGF可能作为内皮细胞存活因子。