ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor, shows antimetastatic activity using a hepatocellular carcinoma model.
The epidermal growth factor receptor (EGFR) is highly expressed in many human tumors and provides a new target for anticancer drug development. EGFR-targeted agents have shown promising antitumor activity in preclinical and clinical trials. However, little is yet known about the effect of these new agents on tumor metastasis. Here, we investigate the effects of ZD1839 (Iressa), a selective EGFR tyrosine kinase inhibitor, on the metastatic properties of murine hepatocellular carcinoma CBO140C12. ZD1839 inhibited not only cell growth but also epidermal growth factor-induced chemotactic migration and production of active matrix metalloproteinase-9 in vitro. In mice, orthotopic implantation of a fragment of CBO140C12 tumor into the liver resulted in the formation of a solitary tumor nodule and intrahepatic metastasis. ZD1839, given p.o., inhibited growth of the implanted tumor and intrahepatic metastasis by approximately 50%. These results indicate that EGFR signaling plays an important role in tumor metastasis and that ZD1839 is effective at inhibiting intrahepatic metastasis.
Matsuo
Mitsuhiro
M
Department of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan.
Sakurai
Hiroaki
H
Saiki
Ikuo
I
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D000077156:Gefitinib; D008113:Liver Neoplasms / Q000188:drug therapy; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D011799:Quinazolines / Q000494:pharmacology*; D015398:Signal Transduction
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib