Gefitinib decreases the synthesis of matrix metalloproteinase and the adhesion to extracellular matrix proteins of colon cancer cells.
BACKGROUND
Adhesion to extracellular matrix (ECM) proteins and degradation of basement membranes by matrix metalloproteinase (MMP) play important roles in cancer metastasis. In this study, the effects of gefitinib on the enzymatic activity of MMP and adhesion to ECM proteins in the HT29 colon cancer cell line were investigated.


METHODS
Microtiter plates, coated with ECM proteins, were used to investigate the adhesion of cancer cells to ECM proteins. The expression of MMPs was examined by zymography and semiquantitative RT-PCR.


RESULTS
Gefitinib inhibited MMP-9 and MMP-2 secretion and mRNA expression in HT29 cells. Gefitinib also reduced the ability to adhere to laminin and type IV collagen. These effects were observed at such low doses that gefitinib had neither an antiproliferative effect nor the ability to induce apoptosis.


CONCLUSIONS
Gefitinib decreased the production of MMPs and the adhesion to ECM proteins, important steps associated with cancer metastasis. These results suggest that gefitinib may have antimetastatic activity in colon cancer.
Department of Cancer and Thoracic Surgery, Graduate School of Medicine and Dentistry, Okayama University, Okayama, Japan. todadkoc@umin.ac.jp
Daisaku
D
Toda
Tetsuya
T
Ota
Kazunori
K
Tsukuda
Keitaro
K
Watanabe
Toshiyuki
T
Fujiyama
Masakazu
M
Murakami
Minoru
M
Naito
Nobuyoshi
N
Shimizu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D000077156:Gefitinib; D019073:HT29 Cells; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D061965:Matrix Metalloproteinase Inhibitors; D011799:Quinazolines / Q000494:pharmacology*
D000970:Antineoplastic Agents; D016326:Extracellular Matrix Proteins; D061965:Matrix Metalloproteinase Inhibitors; D011799:Quinazolines; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077156:Gefitinib