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| 阿伐麦布通过PPARγ诱导细胞周期停滞抑制胶质母细胞瘤细胞增殖及迁移相关机制研究 |
| Study on the mechanism of Avasimibe inhibiting glioblastoma cell proliferation and migration by inducing cell cycle arrest through PPARγ |
| 投稿时间：2026-01-13 修订日期：2026-03-25 |
| DOI： |
| 中文关键词: 阿伐麦布 过氧化物酶体增殖物激活受体γ 细胞周期 胶质母细胞瘤 上皮-间质转化 |
| 英文关键词:Avasimibe peroxisome proliferator-activated receptor gamma cell cycle glioblastoma epithelial-mesenchymal transition |
| 基金项目: |
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| 摘要点击次数: 7 |
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| 中文摘要: |
| 目的 探讨阿伐麦布（Avasimibe）通过过氧化物酶体增殖物激活受体γ（PPARγ）对U251和U87细胞的影响及其机制。方法 U251和U87细胞正常培养不做任何处理设置为Control组。分别采用20 μmol·L-1和30 μmol·L-1的Avasimibe处理U251和U87细胞24 h，设置为Avasimibe组。采用40 μmol·L-1 PPARγ拮抗剂（GW9662）联合20 μmol·L-1 Avasimibe处理U251细胞、采用40 μmol·L-1 GW9662联合30 μmol·L-1 Avasimibe处理U87细胞，设置为Avasimibe+GW9662组。蛋白免疫印迹检测PPARγ、上皮-间质转化（EMT）相关蛋白、细胞周期检查点相关蛋白水平；5-乙炔基-2'-脱氧尿嘧啶核苷（EdU）检测细胞增殖能力；细胞划痕实验检测细胞迁移能力。结果 与Control组相比，Avasimibe组U251和U87细胞的PPARγ蛋白相对表达水平显著升高[（2.02±0.33）比（1.00±0.16）]、[（1.92±0.26）比（1.00±0.19）]（P<0.05）；与Control组相比，Avasimibe组U251和U87细胞增殖率显著降低[（11.32±1.68）%比（45.32±6.04）%]、[（16.33±1.96）%比（51.33±8.12）%]（P<0.05），U251和U87细胞迁移率显著降低[（30.32±5.68）%比（72.32±8.56）%]、[（33.24±5.24）%比（70.33±8.21）%]（P<0.05），U251和U87细胞神经钙黏蛋白（N-Cadherin）蛋白相对表达水平显著降低[（0.35±0.05）比（1.00±0.17）]、[（0.40±0.05）比（1.00±0.15）]（P<0.05），U251和U87细胞细胞周期蛋白依赖性激酶2（CDK2）蛋白相对表达水平显著降低[（0.38±0.05）比（1.00±0.15）]、[（0.35±0.05）比（1.00±0.16）]（P<0.05），U251和U87细胞周期蛋白E1（cyclin E1）蛋白相对表达水平显著降低[（0.52±0.07）比（1.00±0.13）]、[（0.56±0.08）比（1.00±0.14）]（P<0.05）；与Avasimibe组相比，Avasimibe+GW9662组U251和U87细胞增殖率显著升高[（41.22±5.66）%比（11.32±1.68）%]、[（45.33±6.22）%比（16.33±1.96）%]（P<0.05），U251和U87细胞迁移率显著升高[（50.22±7.23）%比（30.32±5.68）%]、[（55.33±8.08）%比（33.24±5.24）%]（P<0.05），U251和U87细胞N-Cadherin蛋白相对表达水平显著升高[（0.77±0.12）比（0.35±0.05）]、[（0.89±0.13）比（0.40±0.05）]（P<0.05），U251和U87细胞CDK2蛋白相对表达水平显著升高[（0.85±0.14）比（0.38±0.05）]、[（0.90±0.14）比（0.35±0.05）]（P<0.05），U251和U87细胞cyclin E1蛋白相对表达水平显著升高[（0.79±0.11）比（0.52±0.07）]、[（0.86±0.15）比（0.56±0.08）]（P<0.05）。结论 Avasimibe通过激活PPARγ，抑制U251和U87细胞增殖、迁移，下调周期蛋白和EMT驱动因子，诱导细胞周期停滞。 |
| 英文摘要: |
| Objective To investigate the effect of Avasimibe on U251 and U87 cells through peroxisome proliferator-activated receptor gamma (PPARγ) and its mechanism. Methods U251 and U87 cells cultured normally without any treatment were set as the Control group. U251 and U87 cells treated with 20 μmol·L-1 and 30 μmol·L-1 Avasimibe for 24 hours were set as the Avasimibe group. U251 cells treated with 40 μmol·L-1 GW9662 combined with 20 μmol·L-1 Avasimibe and U87 cells treated with 40 μmol·L-1 GW9662 combined with 30 μmol·L-1 Avasimibe were set as the Avasimibe+GW9662 group. PPARγ, epithelial-mesenchymal transition (EMT)-related proteins, and cell cycle checkpoint-related protein levels were detected by Western Blot; Cell proliferation ability was detected by 5-ethynyl-2'-deoxyuridine (EdU); Cell migration ability was detected by cell scratch assay. Results Compared with the Control group, the relative expression levels of PPARγ protein in U251 and U87 cells in the Avasimibe group were significantly increased [(2.02±0.33) vs (1.00±0.16)] and [(1.92±0.26) vs (1.00±0.19)] (P<0.05); Compared with the Control group, the proliferation rates of U251 and U87 cells in the Avasimibe group were significantly reduced [(11.32±1.68)% vs (45.32±6.04)%] and [(16.33±1.96)% vs (51.33±8.12)%] (P<0.05), and the migration rates of U251 and U87 cells were significantly reduced [(30.32±5.68)% vs (72.32±8.56)%] and [(33.24±5.24)% vs (70.33±8.21)%] (P<0.05). The relative expression levels of neural cadherin (N-Cadherin) protein in U251 and U87 cells were significantly reduced [(0.35±0.05) vs (1.00±0.17)] and [(0.40±0.05) vs (1.00±0.15)] (P<0.05). The relative expression levels of Cyclin-Dependent Kinase 2 (CDK2) protein in U251 and U87 cells were significantly reduced [(0.38±0.05) vs (1.00±0.15)] and [(0.35±0.05) vs (1.00±0.16)] (P<0.05). The relative expression levels of G1/S-specific cyclin E1 (cyclin E1) protein in U251 and U87 cells were significantly reduced [(0.52±0.07) vs (1.00±0.13)] and [(0.56±0.08) vs (1.00±0.14)] (P<0.05). Compared with the Avasimibe group, the proliferation rates of U251 and U87 cells in the Avasimibe+GW9662 group were significantly increased [(41.22±5.66)% vs (11.32±1.68)%] and [(45.33±6.22)% vs (16.33±1.96)%] (P<0.05), and the migration rates of U251 and U87 cells were significantly increased [(50.22±7.23)% vs (30.32±5.68)%] and [(55.33±8.08)% vs (33.24±5.24)%] (P<0.05). The relative expression levels of N-Cadherin protein in U251 and U87 cells were significantly increased [(0.77±0.12) vs (0.35±0.05)] and [(0.89±0.13) vs (0.40±0.05)] (P<0.05). The relative expression levels of CDK2 protein in U251 and U87 cells were significantly increased [(0.85±0.14) vs (0.38±0.05)] and [(0.90±0.14) vs (0.35±0.05)] (P<0.05). The relative expression levels of cyclin E1 protein in U251 and U87 cells were significantly increased [(0.79±0.11) vs (0.52±0.07)] and [(0.86±0.15) vs (0.56±0.08)] (P<0.05). Conclusion Avasimibe inhibits the proliferation and migration of U251 and U87 cells, down-regulates cyclins and EMT drivers, and induces cell cycle arrest by activating PPARγ. |
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