Cetuximab inhibits growth, peritoneal dissemination, and lymph node and lung metastasis of endometrial cancer, and prolongs host survival.
The purpose of this study was to explore the possibility of molecular-targeted therapy with anti-epidermal growth factor receptor (EGFR) antibody (cetuximab) for endometrial cancer to develop a new treatment for advanced endometrial cancer. We analyzed EGFR protein expression and gene mutations in the human endometrial cancer cell line HEC1A, and evaluated the in vitro and in vivo effects of cetuximab on HEC1A. EGFR expression was observed in HEC1A cells, but no mutations in the EGFR gene were detected. Cetuximab inhibited HEC1A cell growth and invasion and VEGF-A production in vitro, and HECIA cell tumor growth, its peritoneal dissemination with ascites, and lymph node and lung metastasis in vivo. In addition, the antibody prolonged the survival of a mouse model of systemic metastasis. These results suggest the possibility of molecular-targeted therapy using cetuximab for endometrial cancer.
Takahashi
Kayoko
K
Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan.
Saga
Yasushi
Y
Mizukami
Hiroyuki
H
Takei
Yuji
Y
Machida
Shizuo
S
Fujiwara
Hiroyuki
H
Ozawa
Keiya
K
Suzuki
Mitsuaki
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000068818:Cetuximab; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation; D009361:Neoplasm Invasiveness; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab