Selective inhibition of the epidermal growth factor receptor by ZD1839 decreases the growth and invasion of ovarian clear cell adenocarcinoma cells.
The mechanism that regulates the growth of ovarian clearcell adenocarcinoma (CCA) are not well understood. We investigated the role of several growth factors that bind to membrane tyrosine kinase receptors and added them to the ovarian CCA cell lines KK, RMG-1, and HAC-II to evaluate their effect on growth and cellular invasion. Epidermal growth factor and transforming growth factor-alpha significantly stimulated the growth and invasion of CCA cell lines in vitro. ZD1839, an epidermal growth factor receptor-tyrosine kinase inhibitor, decreased the growth and invasion of CCA cell lines in vitro and in vivo inhibited the growth of xenografts of the CCA cell line RMG-1. Severe combined immunodeficient mice bearing RMG-1 xenografts treated with ZD1839 survived for longer than the untreated control group. From these findings, we conclude that ZD1839 may offer a new and effective treatment for ovarian CCA.
Department of Obstetrics and Gynecology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan. masakif@ms.toyamampu.ac.jp
Masaki
M
Fujimura
Takao
T
Hidaka
Shigeru
S
Saito
D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology*; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000970:Antineoplastic Agents; D016207:Cytokines; D016228:Endothelial Growth Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D011799:Quinazolines; D016211:Transforming Growth Factor alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib