论文部分内容阅读
目的探讨大鼠胰腺癌和非癌胰腺组织中EZH2和PTEN的表达水平及其在胰腺癌发生中所起的作用。方法将二甲基苯荓蒽(DMBA)直接置入胰腺实质内制备胰腺癌模型(A,B组),B组成模1周后每周腹腔注射曲古霉素A(TSA)1μg,A,B组3~5个月内处死,对照组(C组)于第5个月处死;肉眼检查和镜下观察胰腺癌发生情况。EnVisionTM免疫组化法检测3组EZH2和PTEN的表达。结果(1)A组3~5个月癌发生率为48.7%(18/37),17例为胰腺导管腺癌,1例为纤维肉瘤;B组3~5个月癌发生率为33.3%(12/36),11例为胰腺导管腺癌,1例为纤维肉瘤;A组胰腺癌最大径均值大于B组(P<0.05);C组胰腺和A,B,2组胰腺外主要脏器均未见明显病理改变。(2)A,B组胰腺导管腺癌EZH2表达阳性率明显高于相应非癌胰腺组织(P<0.01);A组+B组胰腺导管癌PTEN表达阳性率明显低于A组+B组非癌胰腺组织(P<0.05),但A组和B组胰腺导管癌PTEN表达阳性率与A组或B组非癌胰腺组织间差异无统计学意义(P>0.05);EZH2阳性表达和/或PTEN阴性表达的非癌胰腺组织导管上皮均呈轻至重度不典型增生;胰腺导管癌中EZH2与PTEN表达呈明显不一致性(P=0.045);C组正常胰腺EZH2表达均阴性而PTEN表达均阳性。2例纤维肉瘤EZH2和PTEN表达均阴性。结论较大剂量DMBA置入胰实质内可获得较高胰腺癌发生率,TSA能抑制胰腺癌的发生和生长;EZH2基因的激活及PTEN基因的失活在大鼠胰腺癌发生中可能起关键作用。
Objective To investigate the expression of EZH2 and PTEN in rat pancreatic and non-cancerous pancreatic tissues and their roles in pancreatic carcinogenesis. Methods DMBA was directly injected into the parenchyma of the pancreas to prepare pancreatic cancer model (group A, B). One week after model group B, 1 μg of TSA was intraperitoneally injected, Rats in group B were sacrificed within 3 to 5 months, while those in control group (group C) were sacrificed at the 5th month. Macroscopic examination and microscopic observation of pancreatic cancer were performed. EnVisionTM immunohistochemistry was used to detect the expression of EZH2 and PTEN in three groups. Results (1) The incidence of 3 ~ 5 months in group A was 48.7% (18/37), 17 cases of pancreatic ductal adenocarcinoma and 1 case of fibrosarcoma. The incidence of 3 ~ 5 months in group B was 33.3% (12/36), 11 cases of pancreatic ductal adenocarcinoma, 1 case of fibrosarcoma; A group of pancreatic cancer mean diameter greater than the B group (P <0.05); C group of pancreas and A, B, No obvious pathological changes were observed. (2) The positive rate of EZH2 expression in pancreatic ductal adenocarcinoma in group A and group B was significantly higher than that in corresponding non-cancerous pancreatic tissue (P <0.01). The positive rate of PTEN in group A and group B was significantly lower than that in group A and group B (P <0.05). However, the positive rate of PTEN expression in pancreatic ductal carcinoma of group A and group B was not significantly different from that of group A or group B (P> 0.05). The positive expression of EZH2 and / or The expression of EZH2 and PTEN in pancreatic ductal carcinoma was significantly different (P = 0.045). The expression of EZH2 in normal pancreas of group C was negative and the expression of PTEN was positive . Two cases of fibrosarcoma EZH2 and PTEN expression were negative. Conclusion The higher dose of DMBA implanted pancreatic parenchyma can get a higher incidence of pancreatic cancer, TSA can inhibit the occurrence and growth of pancreatic cancer; EZH2 gene activation and PTEN gene inactivation may play a key role in the development of pancreatic cancer in rats .