CAMP/PKA通路在结直肠癌肝转移中的作用及机制研究

目的构建小鼠结直肠癌肝转移模型，探讨CAMP/PKA通路在结直肠癌肝转移中的作用机制。 方法采用皮下成瘤盲肠部位包埋的方法，建立结直肠癌肝转移小鼠模型，随机分为实验组及对照组。实验组模型小鼠连续7天注射CAMP类似物，并于注射完成后7天、14天、28天处死小鼠，采用免疫组化的方法检测两组小鼠原发灶及转移灶内CAMP、PKA、VEGF的表达，采用实时定量PCR的方法检测正常组织及癌组织内MMP2、E-钙粘蛋白的表达。 结果成功建立结直肠癌肝转移小鼠模型，实验组较同期对照组原发灶变小，腹腔及肝脏转移瘤少。两组中转移灶VEGF的表达高于原发灶，癌组织中E-钙粘蛋白表达低于正常组织，MMP2高于正常组织。实验组中随着药物作用时间延长，CAMP、PKA、VEGF、MMP2的表达逐渐变弱。E-钙粘蛋白的表达逐渐升高。 结论CAMP/PKA可通过调节VEGF、E-钙粘蛋白、MMP2的表达，促进结直肠癌发生肝脏转移。

The effect and mechanism of CAMP/PKA pathway in colorectal liver metastases

ObjectiveTo establish a mouse model of colorectal liver metastasis,and to explore the mechanism of CAMP/PKA pathway in colorectal liver metastasis. MethodsTo establish a mouse model of colorectal liver metastasis by embedding subcutaneous tumor in the appendix, and randomly divided into experimental group and control group. The mice of experimental group were injected CAMP analogs for 7 days, the mice were sacrificed in 7 days, 14 days, and 28 days after injection. The expression of CAMP, PKA and VEGF in two groups were detected by immunohistochemical method. The expression of MMP2 and E-cadherin in normal tissue and cancer tissue were detected by quantitative PCR. ResultsIt was succeed to establish a mouse model of colorectal liver metastasis. Comparing to control group, the number of liver metastasis and volume of primary tumor were small in experimental group. The expression of VEGF in the two groups was higher than that in the primary tumor. The expression of E-cadherin in the cancer tissues was lower than that in the normal tissues, and MMP2 was higher than that in the normal tissues. In the experimental group, the expression of CAMP、PKA、VEGF、MMP2 were gradually decreased, while the expression of E-cadherin was increased gradually. ConclusionCAMP/PKA promoted colorectal liver metastasis by regulating the expression of VEGF, E-cadherin and MMP2.