Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Hepatobiliary Pancreat Dis Int. 2010 Dec;9(6):639-44.
Recent studies have confirmed that the expression of Ezrin, hepatocyte growth factor (HGF) and its receptor (C-met) is related to the genesis, progress, invasion and metastasis of some malignant tumors. Researches have also found that the biological function of Ezrin is closely related to HGF/C-met in malignant tumors. However, there is no report on the expression levels of Ezrin, HGF and C-met in rat pancreatic cancer induced by dimethylbenzanthracene (DMBA). This study aimed to detect the expression of Ezrin, HGF and C-met in rat pancreatic cancer and non-cancerous pancreatic tissues, and assess its effect in cancer induction by DMBA.
Ninety Sprague-Dawley rats were divided into 3 groups randomly: 40 in a pancreatic cancer model group (group A), 40 in a trichostatin A (TSA) intervention group (group B), and 10 in a control group (group C). DMBA was directly implanted into the parenchyma of rat pancreas in group A+group B. The rats of group B were treated with 1 ml of TSA saline solution (1 μg/ml) via intraperitoneal injection weekly. The carcinogenesis of rats executed within 3-5 months in groups A and B was observed by macrograph and microscopy. Meanwhile, the rats in group C were executed within 5 months. The EnVisionTM immunohistochemistry for detecting the expression levels of Ezrin, HGF and C-met was used in paraffin-embedded sections of the pancreatic specimens.
The incidence of pancreatic cancer in group A was 48.6% and in group B 33.3%. The maximal diameter of tumor mass was significantly larger in group A than that in group B (P<0.05). No pathological changes were observed in the pancreas of group C and other main organs of groups A and B. The positive rates of Ezrin, HGF and C-met were significantly higher in ductal adenocarcinoma than in non-cancerous pancreatic tissues of groups A and B (P<0.01). The positive rates of Ezrin, HGF and C-met were significantly higher in ductal adenocarcinoma of group A than those in non-cancerous pancreatic tissues of group A (P<0.05), but there was no significant difference in group B (P>0.05). The positive rates of Ezrin, HGF and C-met in non-cancerous pancreatic tissues proved mild to severe atypical hyperplasia of the ductal epithelia. The pancreas of group C and 2 cases of fibrosarcoma showed the negative expression of Ezrin, HGF and C-met. There was a trend of consistency in the expression of Ezrin, HGF and C-met in ductal adenocarcinoma (P<0.05 or P<0.01).
DMBA directly implanted into the parenchyma of the pancreas can produce a model of pancreatic cancer with a high incidence in a short time. TSA might inhibit the carcinogenesis and growth of pancreatic cancer, and its effects may be related to the inhibition of the expression of Ezrin, HGF and C-met during the process. Ezrin, HGF and C-met may have positive effects on the carcinogenesis of rat pancreas.
最近的研究证实，埃兹蛋白（Ezrin）、肝细胞生长因子（HGF）及其受体（C-met）的表达与某些恶性肿瘤的发生、发展、侵袭和转移有关。研究还发现，Ezrin 的生物学功能与恶性肿瘤中的 HGF/C-met 密切相关。然而，关于二苯并蒽（DMBA）诱导的大鼠胰腺癌中 Ezrin、HGF 和 C-met 的表达水平尚无报道。本研究旨在检测 Ezrin、HGF 和 C-met 在大鼠胰腺癌和非癌胰腺组织中的表达，并评估其在 DMBA 诱导癌症中的作用。
将 90 只 Sprague-Dawley 大鼠随机分为 3 组：胰腺癌模型组（A 组）40 只，曲古抑菌素 A（TSA）干预组（B 组）40 只，对照组（C 组）10 只。A 组和 B 组直接将 DMBA 植入胰腺实质。B 组大鼠每周通过腹腔注射 1 毫升 1μg/ml 的 TSA 生理盐水进行治疗。观察 A 组和 B 组大鼠在 3-5 个月内的致癌作用，并通过肉眼和显微镜观察。同时，C 组大鼠在 5 个月内执行。使用 EnVisionTM 免疫组织化学检测胰腺标本石蜡包埋切片中 Ezrin、HGF 和 C-met 的表达水平。
A 组胰腺癌的发病率为 48.6%，B 组为 33.3%。A 组肿瘤块的最大直径明显大于 B 组（P<0.05）。A 组和 B 组的胰腺和其他主要器官均未观察到病理变化。A 组和 B 组导管腺癌中 Ezrin、HGF 和 C-met 的阳性率明显高于非癌胰腺组织（P<0.01）。A 组导管腺癌中 Ezrin、HGF 和 C-met 的阳性率明显高于 A 组非癌胰腺组织（P<0.05），但 B 组无显著差异（P>0.05）。A 组非癌胰腺组织中 Ezrin、HGF 和 C-met 的阳性率表现为导管上皮的轻度至重度非典型增生。C 组胰腺和 2 例纤维肉瘤显示 Ezrin、HGF 和 C-met 的阴性表达。导管腺癌中 Ezrin、HGF 和 C-met 的表达呈一致性趋势（P<0.05 或 P<0.01）。
DMBA 直接植入胰腺实质可在短时间内产生高发生率的胰腺癌模型。TSA 可能抑制胰腺癌的发生和生长，其作用可能与抑制 Ezrin、HGF 和 C-met 的表达有关。Ezrin、HGF 和 C-met 可能对大鼠胰腺的癌变有积极作用。
