活血化瘀药对不同阶段肺癌微转移的影响及其作用机制的研究

项目名称： 活血化瘀药对不同阶段肺癌微转移的影响及其作用机制的研究

项目编号： No.30873334

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 张培彤

作者单位： 中国中医科学院广安门医院

项目金额： 30万元

中文摘要： 本课题以活血化瘀中药对不同阶段肺癌微转移的影响作为研究方向，分体内、体外实验两部分，体内实验模拟早、中、晚期肺癌的动物模型采用不同类别活血药干预；体外实验以不同氧浓度细胞环境模拟肿瘤不同阶段生长状态，通过检测细胞CD44V6、CD29、CD44S、HIF-1a等分子表达水平，从影响内皮细胞通透性及细胞粘附等角度探讨活血药对肺癌微转移的影响。结果显示：活血药在抑瘤率和抑转移率方面效果较对照组好，其中，苏木作用最好。苏木各组均抑制小鼠CD44、P-select、CK18、CK19等分子的表达水平，且高剂量苏木联合环磷酰胺组在早期作用效果最强，提示苏木有抑制微转移作用；在体外实验中，活血药川芎嗪、丹参、苏木均可不同程度抑制PG细胞的增殖和侵袭能力，且可下调CD29、CD44S、CD44v6、HIF-1等分子表达水平，提示活血药可能从抑制PG增殖、侵袭和粘附等角度抑制微转移，且低氧环境有可能是促进转移的有利因素。在裸鼠自发转移实验中亦证实，活血药干预下的PG细胞其自发转移能力减弱。

中文关键词： 肺癌；微转移；分子机制；乏氧环境

英文摘要： This research focus on the influence of blood-activating Chinese medicine on micrometastases of lung cancer which in different phases. The reserch includes esoteric and exosomatic experiment. The esoteric experiments simulate the early, metaphase and terminal stages of lung cancer on animal models for different kinds of blood-activating medicine intervention and together with chemo-treatment. And the exosomatic experiments simulate the different oxygen concentration rates environments for different stages of tumors, using MTT, ELASA, FCM and immune fluorescent technique to testify cells CD44V6, CD29, CD44S and HIF-1a indexes, and research the activating medicine effects on the micrometastases from the endothelial cell permeability and the cell adhesion. Experiment results show that the blood-activating medicine works better on inhibition of tumor development and metastasis than the control group.And sandwood plays best among the four medicine.Every group that includs sandwood can decrease the expression of such molecule as CD44S, P-select,CK18 and CK19.What's more, the high concentration of sapanwood-cyclophosphamide group went strongest in the early stage .All above can imply that sandwood can inhabit the micrometastases of lung cancer. In the exosomatic experiments, the blood-activating medicine sandwood, ligustrazine and tanshinone can restrain the multiplication and invasion of PG cells.Besides,the three blood-activiting medicine can inhabit the espression of such molecule as CD44s,CD44V6,HIF-1a and CD29,which can point out that blood-activiting medicine can restrain the micrometastases of lung cancer by inheibt the mutiplication,invasion and adhesion of the tumour cells.Finally, the self-metastasis experiments of nude mouse can also demonstrate that PG cells which intervened by blood-activiting medicine have a inferior self-metastasis.

英文关键词： lung cancer;micro metastases;molecule mechanism;low oxygen environment