重楼调控PI3K/AKT信号通路诱导细胞自噬抗宫颈癌血管生成的作用研究

Tumor vascular targeting therapy has been gradually developing as one of the main study directions nowadays in the field of tumor research. The innovation of the traditional chinese medicine in recent years have broadened the scope and therapeutic effect of tumor therapy, the hotspot and breakthrough of research on tumor is seeking new tumor angiogenesis drugs from natural plants as well as traditional chinese medicine (TCM) . Previous studies in the project group found that Rhizoma Paris has inhibitory effect on angiogenesis of cervical cancer and can induce autophagy of cervical cancer cells.Based on theprevious researches, this task studies the effects of rhizoma paridis, an active ingredient in TCM, on cervical carcinoma angiogenesis and the possible mechanism, explore what role does PI3K/Akt signaling pathways play in the progress of rhizoma paridis repelling angiogenesis. This task designs to study the farther mechanism from both in vivo and in vitro by using molecular biology, pharmacology, pathology detection and other means, while with the help of co-culture of Hela cells and human umbilical vein endothelial cells, gene protein expression detection relatingto angiogenesis, modeling a nude mouse transplanted tumor and histopathological examinations; as well as using cell signal transduction pathway inhibitors and gene interference technology to silence key gene. This study could promote certain theoretical basis and experimental evidence to explore an effective anti-tumor angiogenesis of TCM, furthermore, could build a promising beginning for searching the next step of developing new anti-angiogenesis drugs from traditional Chinese medicine.

肿瘤血管靶向治疗已逐步发展成为当今肿瘤领域研究的主攻方向之一。近年来中医药的创新拓宽了肿瘤治疗的范围和效果，从天然植物或中药中寻找新型抗肿瘤血管生成药物是肿瘤研究的热点和突破口。项目组前期研究发现中药重楼对宫颈癌血管生成具有抑制作用，且能诱导细胞发生自噬，本课题在前期基础上探讨PI3K/Akt信号通路在重楼诱导细胞自噬抗宫颈癌血管生成中的作用。课题设计从体内外两部分着手，采用分子生物学、药理学及病理学检测等手段，通过Hela细胞与人脐静脉内皮细胞共培养、血管生成相关基因蛋白表达检测、裸鼠移植瘤模型的建立及组织病理学检测等指标；运用细胞信号转导通路抑制剂以及基因干扰技术沉默关键基因等方法研究重楼深入的作用机制。通过本研究可以为寻找有效的抗肿瘤血管生成中药提供一定的理论基础和实验依据，并为下一步从中药中开发抗肿瘤血管生成新药创造了良好的开端。

肿瘤血管靶向治疗已逐步发展成为当今肿瘤领域研究的主攻方向之一。近年来中医药的创新拓宽了肿瘤治疗的范围和效果，从天然植物或中药中寻找新型抗肿瘤血管生成药物是肿瘤研究的热点和突破口。项目组前期研究发现中药重楼对宫颈癌血管生成具有抑制作用，且能诱导细胞发生自噬，本课题在前期基础上探讨PI3K/Akt信号通路在重楼诱导细胞自噬抗宫颈癌血管生成中的作用。课题设计从体内外两部分着手，采用分子生物学、药理学及病理学检测等手段，通过Hela细胞与人脐静脉内皮细胞共培养模拟肿瘤血管生成微环境、血管生成相关基因白表达检测、裸鼠移植瘤模型的建立及组织病理学检测等指标；运用细胞信号转导通路抑制剂以及基因干扰技术沉默关键基因等方法研究重楼深入的作用机制。项目研究阐明了重楼皂苷Ⅱ抑制了宫颈癌血管生成，其可能机制是通过诱导肿瘤相关血管内皮细胞发生自噬性死亡，自噬的调控可能是通过调控PI3K/AKT/mTOR信号通路完成的。通过本研究可以为寻找有效的抗肿瘤血管生成中药提供一定的理论基础和实验依据，并为下一步从中药中开发抗肿瘤血管生成新药创造了良好的开端。