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항-표피성장인자수용체 단클론항체와 DNA 토포이소머라제 억제제에 의한 마우스 모델에서의 타액선 선낭암종 성장 억제

Anti-epidermal growth factor receptor (EGFR) monoclonal antibody and DNA topoisomerase inhibitor reduce growth of salivary adenoid cystic carcinoma in a murine model

대한구강악안면외과학회지 2010년 36권 3호 p.177 ~ 185
박영욱 ( Park Young-Wook ) - 강릉원주대학교 치과대학 구강악안면외과학교실

이희수 ( Lee Hee-Su ) - 강릉원주대학교 치과대학 구강해부학교실


EGFR을 발현하는 인간 타액선 선낭암 세포주를 면역결핍 마우스에 이종이식한 후 Erbitux와 CPT-11을 적용하여 단독치료 또는 복합치료를 5주간 시행하였다. 실험동물 희생 후 부검(necropsy)을 통하여 조직학적 관찰을 시행하고, 마우스 종물에 대한 면역조직화학염색과 TUNEL 분석을 통하여 다음과 같은 결과를 도출하였다. 1. Erbitux, CPT-11, Erbitux/CPT-11 치료군은 대조군과 비교하여 종양 증식이 각각 22, 70, 74 % 감소하였다. 2. CPT-11 치료에 의하여 종양세포의 아포프토시스가 유도되었으며, 동시에 종물의 미세혈관밀도가 감소되었다.(P<0.05) 3. CPT-11에 의한 종양 증식 억제와 종양세포의 아포프토시스 유도 효과는 Erbitux에 의하여 상승되지 않았다. 4. CPT-11 치료나 Erbitux/CPT-11 치료에 의하여 종양관련 내피세포의 아포프토시스는 유도되지 않았다.(P<0.05)

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 ㎎) two times per week, intraperitoneal Irinotecan (50 ㎎/㎏) 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.


Monoclonal antibodies;Epidermal growth factor receptor;DNA topoisomerases type 1;Adenoid cystic carcinoma;Salivary gland neoplasms;Parotid neoplasms
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