抗表皮生长因子受体单克隆抗体对人胰腺癌裸鼠模型的化疗增敏作用

目的 观察鼠抗人EGFR单克隆抗体联合5-氟尿嘧啶(5-Fu)、健择对裸鼠胰腺癌化疗效果的影响.方法 将人胰腺癌肿瘤细胞悬液注射于裸鼠背部皮下,建立肿瘤模型.干预组腹腔分别注射鼠抗人EGFR单克隆抗体(MMAb-2)、5-Fu、健择及其配伍联合用药;对照组腹腔注射生理盐水.干预4周后处死裸鼠,切取肿瘤,测量瘤体积,取肿瘤组织送病理学检查;免疫组化法检测肿瘤组织中bax、bcl-2的表达;免疫荧光法检测肿瘤组织中细胞凋亡指数,评价干预效果.结果 5-Fu、健择联合应用MMAb-2对裸鼠胰腺癌细胞增殖的抑制作用明显增强(P＜0.05),且能提高裸鼠胰腺癌细胞凋亡率(P＜0.05).结论 抗EGFR单克隆抗体能有效提高化疗药物5-Fu、健择对裸鼠胰腺癌细胞抑制作用的敏感性,可明显提高胰腺癌的化疗效果.

Enhanced effect of anti-EGFR monoclonal antibody ( MMAb-2 ) on sensitivity of regular chemotherapeutic agent of pancreatic cancer in nude mice model

Objective To study the effect of anti-EGFR monoclonal antibody (MMAb-2) on chemosensitivity of pancreatic cancer in combination with chemotherapeutic agent. Methods A tumor cell suspension (SW1990) was injected into the subcutaneous dorsa of mice in the proximal midline. The treatment groups received intraperitoneal injections of MMAb-2 or 5-Fu or gemcitabine or MMAb-2, 5-Fu and gemcitabine in combination respectively. The control group only received intraperitoneal injection of saline.After treatment for 4 weeks, the mice were killed, and tumors were excised. The size of the pancreatic tumors was recorded. Histopathology confirmed the identity of the disease. The expression of bax and bcl-2 in the resected pancreatic tissue was detected by immunohistochemistry. Tumor tissues were examined by immunofluorescence for apoptosis. Results The inhibition rate of proliferation in pancreatic tumor cells was increased evidently by 5-Fu, gemcitabine in combination with MMAb-2 ( P ＜ 0. 05 ), and MMAb-2 also increased the apoptosis rate in pancreatic tumor cells (P ＜ 0. 05). Conclusion The MMAb-2 could enhance significantly the sensitivity of the cyto-inhibition of the chemotherapeutic agents on pancreatic tumor cells, and could improve the chemotherapeutic effect of pancreatic cancer.