Inhibited growth of colon cancer carcinomatosis by antibodies to vascular endothelial and epidermal growth factor receptors.
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.
Shaheen
R M
RM
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard-444, Houston, TX 77030, USA.
Ahmad
S A
SA
Liu
W
W
Reinmuth
N
N
Jung
Y D
YD
Tseng
W W
WW
Drazan
K E
KE
Bucana
C D
CD
Hicklin
D J
DJ
Ellis
L M
LM
D000818:Animals; D017209:Apoptosis; D001201:Ascites / Q000276:immunology / Q000503:physiopathology; D002277:Carcinoma / Q000276:immunology* / Q000556:secondary; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000494:pharmacology*; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000502:physiology; D008222:Lymphokines / Q000096:biosynthesis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic; D010534:Peritoneal Neoplasms / Q000276:immunology* / Q000556:secondary; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D066246:ErbB Receptors