Antitumor Activity of Gefitinib in Malignant Rhabdoid Tumor Cells In vitro and In vivo

• DOI: 10.1158/1078-0432.ccr-04-0192
• Publication Date: 2005-09-21T23:58:40Z
• Authors: Yasumichi Kuwahara; Hajime Hosoi; Shinya Osone; Masakazu Kita; Tomoko Iehara; Hiroshi Kuroda; Tohru Sugimoto
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Immunoblotting; Transplantation, Heterologous; Fluorescent Antibody Technique; Infant; Mice, Nude; Antineoplastic Agents; Apoptosis; Gefitinib; In Vitro Techniques; 3. Good health; ErbB Receptors; Immunoenzyme Techniques; Mice; 03 medical and health sciences; Quinazolines; Animals; Humans; Female; Phosphorylation; Cell Division; Rhabdoid Tumor

Abstract Purpose: Malignant rhabdoid tumor (MRT) is a rare and highly aggressive neoplasm of young children. Current treatments have had only limited success. Epidermal growth factor receptor (EGFR) was found recently to be expressed on MRT cell lines. Gefitinib (trade name Iressa) an oral selective EGFR-tyrosine kinase inhibitor has been demonstrated effective in inhibiting the proliferation cancer cells vivo as well clinical trials. This encouraged us examine antitumor effects gefitinib vitro vivo. Experimental Design: The expression EGFR two tumors lines (MP-MRT-AN KP-MRT-NS), established from these tissues, examined by immunohistochemistry, immunofluorescence, immunoblot. effect phosphorylation apoptosis were assay terminal deoxynucleotidyl transferase-mediated nick end labeling assay. assessed athymic mice that xenografted with cells. Results: detected both tissues inhibited EGFR-phosphorylation (IC50 < 0.1 μmol/L) = approximately 10–12 μmol/L), high concentration (20 induced (MP-MRT-AN, 42.9% KP-MRT-NS, 47.2%). Furthermore, at 150 mg/kg cytostatic xenografts P 0.039 0.0014; 0.048 0.0086). Conclusions: Our results demonstrate and, thus, promise novel therapeutic strategy for MRT.