Sun Ji, Wang Kai, Teng Jingfei, Yu Yufu, Hua Runmiao, Zhou Haiyong, Zhong Dachuan, Fan Yi
Department of Urology, Zhejiang Xiaoshan Hospital, Hangzhou, Zhejiang 311202, China.
Department of Urology, PLA Army General Hospital, Beijing, 100700, China.
Biomed Pharmacother. 2017 Aug;92:108-115. doi: 10.1016/j.biopha.2017.04.134. Epub 2017 May 19.
The aim of this study was to explain the Numb anti-cancer effects in the prostatic cancer.
Collecting the 20 prostatic cancer patients and analyzing the correlation between Numb and Glease score. Transfection Numb into DU-145 and PC-3 cells, measuring the proliferation rate of difference groups by MTT assay, evaluating the cell apoptosis and cell cycle of difference group by Flow cytometry; measuring the invasion and migration abilities by transwell and wound healing assays. In the nude mice experiment, establish prostatic cancer nude mouse subcutaneous planting tumor model by DU-145 cells, Injection the Numb from tail vein. Evaluating the tumor volume and weight.
The Numb protein expression was decreased with Glease score increasing. The proliferation rate of Numb groups were significantly decreased compared with NC groups (P<0.05, respectively). The apoptosis and G1 phase rates of Numb groups were significantly enhanced compared with NC groups (P<0.05, respectively). The invasion and migration abilities of Numb group cells were significantly weaken compared with NC groups (P<0.05, respectively). In the WB assay, The relative proteins (Numb, P53, Cyclin D1, Rac1, MMP-2 and MMP-9) expression were significantly differences between NC and Numb groups (P<0.05, respectively). In the vivo experiment, the tumor volume and weight of Numb group was significantly lighter than NC group (P<0.05, respectively).
Overexpression Numb had anti-cancer effects to prostatic cancer in vitro and vivo experiments, the mechanism might be P53/Cyclin D1 and Rac1/MMP-2/-9 signaling pathway.
本研究旨在阐释Numb在前列腺癌中的抗癌作用。
收集20例前列腺癌患者，分析Numb与Gleason评分之间的相关性。将Numb转染至DU-145和PC-3细胞中，通过MTT法检测不同组的增殖率，通过流式细胞术评估不同组的细胞凋亡和细胞周期；通过Transwell和伤口愈合试验检测侵袭和迁移能力。在裸鼠实验中，用DU-145细胞建立前列腺癌裸鼠皮下种植瘤模型，尾静脉注射Numb。评估肿瘤体积和重量。
Numb蛋白表达随Gleason评分增加而降低。与NC组相比，Numb组的增殖率显著降低（分别为P<0.05）。与NC组相比，Numb组的凋亡率和G1期比例显著升高（分别为P<0.05）。与NC组相比，Numb组细胞的侵袭和迁移能力显著减弱（分别为P<0.05）。在WB检测中，NC组和Numb组之间的相关蛋白（Numb、P53、细胞周期蛋白D1、Rac1、基质金属蛋白酶-2和基质金属蛋白酶-9）表达存在显著差异（分别为P<0.05）。在体内实验中，Numb组的肿瘤体积和重量明显轻于NC组（分别为P<0.05）。
在体外和体内实验中，Numb过表达对前列腺癌具有抗癌作用，其机制可能是P53/细胞周期蛋白D1和Rac1/基质金属蛋白酶-2/-9信号通路。
