Anti-epidermal growth factor receptor (EGFR) monoclonal antibody and DNA topoisomerase inhibitor reduce growth of salivary adenoid cystic carcinoma in a murine model.
10.5125/jkaoms.2010.36.3.177
- Author:
Young Wook PARK
1
;
Hee Su LEE
Author Information
1. Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung, Korea. ywpark@gwnu.ac.kr
- Publication Type:Original Article
- Keywords:
Monoclonal antibodies;
Epidermal growth factor receptor;
DNA topoisomerases type 1;
Adenoid cystic carcinoma;
Salivary gland neoplasms;
Parotid neoplasms
- MeSH:
Adenoids;
Animals;
Antibodies, Monoclonal;
Antibodies, Monoclonal, Humanized;
Apoptosis;
Camptothecin;
Carcinoma, Adenoid Cystic;
Cell Line;
Cetuximab;
DNA;
DNA Topoisomerases, Type I;
Humans;
Mice;
Mice, Nude;
Microvessels;
Parotid Neoplasms;
Receptor, Epidermal Growth Factor;
Salivary Gland Neoplasms;
Tumor Burden
- From:Journal of the Korean Association of Oral and Maxillofacial Surgeons
2010;36(3):177-185
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
INTRODUCTION: Epidermal growth factor receptor (EGFR) is expressed in human epithelial tumors including salivary cancers, and known to be correlated with tumor progression and poor clinical courses in some epithelial tumors. In this study, we determined the therapeutic effect of the anti-EGFR monoclonal antibody Erbitux (C225, cetuximab) in combination with the DNA topoisomerase I inhibitor irinotecan (CPT-11) on human salivary adenoid cystic carcinoma (SACC) cells growing in nude mice. MATERIALS AND METHODS: At first, immunocytochemical analysis for the expression of EGFR and phosphorylated EGFR (pEGFR) on a human salivary ACC cell line (ACC3). To determine the in vivo effects of Erbitux and CPT-11, nude mice with orthotopic parotid tumors were randomized to receive intraperitoneal Erbitux (1 mg) two times per week, intraperitoneal Irinotecan (50 mg/kg) once per week, Erbitux plus CPT-11, or placebo. (control) Tumor volume and weight were measured. And mechanisms of in vivo activity of Erbitux and/or CPT-11 were determined by immunohistochemical/immunofluorescent analyses. RESULTS: Immunocytochemical staining of ACC3 demonstrated that EGFR was expressed and phosphorylated. CPT-11 inhibited ACC tumor growth in nude mice. Tumors of mice treated with CPT-11 and CPT-11 plus Erbitux exhibited increased tumor cell apoptosis and decreased microvessel density, which correlated with a decrease in the tumor volume in nude mice. But, CPT-11 seems not to be synergistic with Erbitux in our ACC3 model system. CONCLUSION: These results suggest that anti-EGFR monoclonal antibody and the DNA topoisomerase I inhibitor will be effective in the treatment of recurred or metastatic lesions of salivary ACC.
