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目的:建立SD大鼠胰腺癌模型,观察曲古霉素A(TSA)对二甲基苯荓蒽(DMBA)诱癌的抑制作用,探讨Ezrin、HGF和C-met表达与胰腺癌发生发展的相关性。方法:90只SD大鼠随机分为3组,DMBA置入胰腺实质内(A组+B组),B组每周腹腔注射TSA1μg;A组和B组于3～5个月内处死,对照组(C组)于第5个月处死。Ezrin、HGF和C-met染色方法均为石蜡切片EnVisionTM免疫组化法。结果:1)A组癌发生率为48.7%;B组癌发生率为33.3%;A组胰腺癌最大径均值>B组,P<0.05;C组胰腺和A、B两组胰腺外主要脏器均未见明显病理改变;2)A组+B组胰腺导管癌Ezrin、HGF和C-met阳性表达率明显高于A组+B组非癌胰腺组织,P<0.01;A组胰腺导管癌Ezrin、HGF和C-met阳性表达率明显高于A组非癌胰腺组织(P<0.05),C组胰腺和2例纤维肉瘤Ezrin、HGF和C-met均为阴性表达;Ezrin、HGF和C-met在胰腺导管癌中表达呈一致性,P<0.05。结论:较大剂量DMBA置入胰腺实质内可获得较高胰腺癌发生率;Ezrin、HGF和C-met在DMBA诱癌过程中可能有重要促癌发生作用;TSA能抑制胰腺癌发生和生长,其机制可能与抑制Ezrin、HGF和C-met表达有关。
OBJECTIVE: To establish a rat model of SD rat pancreatic cancer and observe the inhibitory effect of TSA on DMBA-induced pancreatic cancer and to explore the relationship between the expression of Ezrin, HGF, C-met and the development of pancreatic cancer Correlation. Methods: Ninety Sprague-Dawley rats were randomly divided into three groups: DMBA was injected into the parenchyma of the pancreas (group A + B), and group B was intraperitoneally injected with TSA 1 μg per week. A and B groups were sacrificed within 3 to 5 months. Group C (Group C) was sacrificed on the 5th month. Ezrin, HGF and C-met staining methods were paraffin-embedded EnVisionTM immunohistochemistry. Results: 1) The incidence of cancer in group A was 48.7%; The incidence of cancer in group B was 33.3%; The mean diameter of pancreatic cancer in group A was> B, P <0.05; 2) The positive expression rates of Ezrin, HGF and C-met in group A and group B were significantly higher than those in group A and group B (P <0.01); Group A pancreatic ductal carcinoma The positive rates of Ezrin, HGF and C-met were significantly higher in group A than those in group A (P <0.05). The expressions of Ezrin, HGF and C-met in pancreas and 2 fibrosarcoma in group C were negative. -met expression was consistent in pancreatic ductal carcinoma, P <0.05. Conclusions: Higher doses of DMBA can induce higher pancreatic cancer incidence in pancreatic parenchyma. Ezrin, HGF and C-met may play an important role in carcinogenesis of DMBA; TSA can inhibit the occurrence and growth of pancreatic cancer, The mechanism may be related to the inhibition of Ezrin, HGF and C-met expression.