endocan对胃癌细胞生物学行为的影响及其机制的研究

The dysfunction of many proteins are involved in the tumorigenesis and development of carcinomas.We found an abnormal expression of endocan in many neoplasms when we explored mechanism of tumor metastasis. There is an obvious high endocan expression in many malignant tumors such as renal cancer, lung cancer,liver cancer,breast cancer and acute leukemia. And endocan expression value has a positive correlation with the degree of malignancy, metastasis potential and angiogenesis. But expression of endocan was signi?cantly decreased in tissues of gastric cancer and colorectal cancer as compared to normal gastric and colorectal tissues. There is correlation between the degree of the decrease of endocan expression and the degree of differentiation of the cancer. In this project, the effects of endocan on the biological behaviors including proliferation,apoptosis and migration of gastric cancer cell line SGC 7901 and BGC 823 and its tumorigenesis and metastasis ability in vivo will be investigated. And the molecular mechanisms of how endocan play roles in gastric cancer cells will be revealed preliminarily.Thus the roles of endocan on the tumorigenesis and development of gastric cancer will be analyzed. And then we could speculate if endocan might be a target protein in gastric cancer treatment. This will provide new ideas for further study the functions of endocan.

肿瘤的发生、发展与多种蛋白质质与量的变化及其调控失衡密切相关，我们在研究肿瘤转移机制时，有趣地发现endocan在许多肿瘤中表达异常。国内外研究报道在肾癌、肺癌、肝癌、乳腺癌、急性白血病等肿瘤中，endocan表达量明显增加并且其表达量与肿瘤恶性程度和转移以及血管生成呈正相关，而在胃癌和结肠癌中endocan的表达较正常组织明显减少，其表达和分化程度呈正相关。而endocan在胃癌发生、发展中的作用及机制尚不清楚。本项目将探讨endocan对胃癌细胞系SGC 7901和BGC 823的增殖、凋亡、迁移等生物学行为的影响以及endocan表达改变对胃癌细胞体内成瘤和转移能力的影响，并初步探讨endocan发挥作用的可能分子机制，分析endocan在胃癌发生、发展中的作用，明确endocan作为靶蛋白治疗胃癌的可能性，并为进一步探讨endocan的功能提供思路.

结题摘要..肿瘤的发生、发展与多种蛋白质质与量的变化及其调控失衡密切相关，我们在研究肿瘤转移机制时，有趣地发现endocan在许多肿瘤中表达异常。国内外研究报道在肾癌、肺癌、肝癌、乳腺癌、急性白血病等肿瘤中，endocan表达量明显增加并且其表达量与肿瘤恶性程度和转移以及血管生成呈正相关，而在胃癌和结肠癌中endocan的表达较正常组织明显减少，其表达和分化程度呈正相关。而endocan在胃癌发生、发展中的作用及机制尚不清楚。本项目将探讨endocan对胃癌细胞系SGC 7901和BGC 823的增殖、凋亡、迁移等生物学行为的影响以及endocan表达改变对胃癌细胞体内成瘤和转移能力的影响，并初步探讨endocan发挥作用的可能分子机制，分析endocan在胃癌发生、发展中的作用，明确endocan作为靶蛋白治疗胃癌的可能性，并为进一步探讨endocan的功能提供思路。成功构建endocan过表达慢病毒载体和endocan RNAi慢病毒载体，测序结果显示均构建成功。将感染至胃腺癌细胞中，获得稳定转染的细胞株。Endocan表达水平与胃腺癌细胞的分化水平、迁移能力等明显相关。细胞形态学分析和胃癌分化标志酶检测结果均提示，endocan过表达的细胞其分化程度明显升高，而endocan低表达的细胞则显示出低分化的细胞特征。细胞迁移实验结果显示，和对照细胞相比较，endocan过表达的细胞其迁移能力明显下降，迁移距离明显低于对照组细胞，而endocan低表达细胞的迁移距离明显增加，迁移能力明显高于对照细胞。同时，endocan通过调节Bcl-2/Bax比例而调节胃癌细胞SGC7901凋亡水平。用endocan高表达和低表达的SGC7901细胞行裸鼠荷瘤实验，结果显示，endocan高表达能明显降低SGC7901细胞的体内成瘤能力。.以上结果表明，endocan表达水平明显影响胃腺癌细胞的生物学行为，其高表达使胃腺癌细胞恶性程度下降，而低表达时则细胞恶性程度增加，提示endocan可以作为胃癌恶性程度的预测指标，并且可能作为胃癌诱导分化治疗的靶点之一。