Notch-1阻断剂对骨肉瘤小鼠模型肿瘤生长的抑制作用及相关分子机制探究

Inhibiting effect of Notch-1 blocker on tumor growth in osteosarcoma mouse models as well as related molecular mechanisms

目的:Notch-1阻断剂对骨肉瘤小鼠模型肿瘤生长的抑制作用及相关分子机制。方法:选择SCID小鼠作为实验对象,皮下注射骨肉瘤细胞以建立骨肉瘤小鼠模型,分为GSI组、PBS组并分别位于GSI、PBS干预。干预后第0d、5d、10d、15d和20d时,测定肿瘤组织的体积;干预后第20d时,测定肿瘤组织中促凋亡、促增殖以及侵袭相关分子的含量。结果:干预第0d时,GSI组小鼠的肿瘤体积与PBS组比较无显著差异;干预后5d、10d、15d和20d时,GSI组小鼠的肿瘤体积均显著小于PBS组;干预后第20d时,GSI组小鼠肿瘤组织中促增殖分子AEG-1、Orai1、STIM1、PAK5、RIPK4、β-catenin以及促侵袭分子Gab2、DLK1、Scr、B7-H3的含量显著低于PBS组,促凋亡分子RanBP9、PD-1、PDL1、PD-L2以及侵袭抑制分子TIMP1、TIMP2的含量显著高于PBS组。结论:Notch-1阻断剂能够抑制骨肉瘤小鼠模型肿瘤的生长,参与这一过程的分子机制包括降低促增殖分子和促侵袭分子的生成、增加促凋亡和侵袭抑制分子的生成。

Objective：To explore the inhibiting effect of Notch-1blocker on tumor growth in osteosarcoma mouse models as well as related molecular mechanisms.Methods：SCID mice were selected as experimental subjects,and osteosarcoma mouse models were built through subcutaneous injection of osteosarcoma cells and divided into GSI group and PBS group who received GSI and PBS intervention respectively.0d,5d,10 d,15dand 20 dafter intervention,tumor tissue volume was detected;20dafter intervention,the contents of pro-apoptosis,pro-proliferation and invasion-related molecules in tumor tissue were detected.Results：0dof intervention,tumor volume of GSI group was not significantly different from that of PBS group;5d,10 d,15dand 20 dafter intervention,tumor volume of GSI group was significantly lower than that of PBS group;20dafter intervention,the contents of pro-proliferation molecules AEG-1,Orai1,STIM1,PAK5,RIPK4andβ-catenin as well as invasion-promoting molecules Gab2,DLK1,Scr and B7-H3 in tumor tissue of GSI group were significantly lower than those of PBS group,and the contents of pro-apoptosis molecules RanBP9,PD-1,PD-L1 and PD-L2 as well as invasion-inhibiting molecules TIMP1 and TIMP2were significantly higher than those of PBS group.Conclusions：Notch-1blocker can inhibit tumor growth in osteosarcoma mouse models,and the molecular mechanisms involved in the process include reducing the generation of pro-proliferation molecules and invasion-promoting molecules and increasing the generation of pro-apoptosis and invasion-inhibiting molecules.