| 赵兰夫 吕文海 陈隆 张玉富 郑涛 贺世明.PI3K通路抑制剂LY294002
对人脑胶质瘤细胞株U87 细胞衰老和凋亡的影响[J].,2014,14(11):2011-2014 |
| PI3K通路抑制剂LY294002
对人脑胶质瘤细胞株U87 细胞衰老和凋亡的影响 |
| Effect of PI3K pathway inhibitor LY294002on cellular senescence and apoptosis of U87 human glioma cell line |
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| DOI： |
| 中文关键词: PI3K通路 抑制剂 LY294002 细胞衰老 凋亡 |
| 英文关键词: PI3K pathway inhibitor LY294002 Cellular senescence Apoptosis |
| 基金项目: |
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| 中文摘要: |
| 目的：PI3K/Akt信号通路是与胶质瘤发生发展密切相关的核心通路之一，LY294002 是该通路的特异性抑制剂。本研究通过
探讨PI3K通路抑制剂LY294002 对U87 胶质瘤细胞系细胞衰老及凋亡的影响，从而为胶质瘤患者治疗的新策略奠定理论基础。
方法：将体外培养的人脑胶质瘤U87 细胞株分为DMSO 处理的对照组和LY294002（100 滋M）处理的实验组，采用茁- 半乳糖苷酶
染色和流式细胞术的方法，分别检测并比较两组肿瘤细胞衰老和凋亡的情况。结果：LY294002 处理组U87 胶质瘤细胞的衰老指
数（32.20± 4.46%）显著高于DMSO 对照组（3.40± 1.61%，t=6.254，P＜0.001）。另外，与DMSO 对照组相比，凋亡蛋白caspase-3
mRNA 的表达在LY294002 处理组胶质瘤细胞中显著上调（t=8.923，P＜0.05）。LY294002 处理组肿瘤细胞的凋亡指数（80.10±
4.832%）明显高于DMSO 对照组（4.260± 1.073%，t=8.923，P＜0.05）。结论：LY294002 既能够诱导肿瘤细胞衰老，又能够诱导肿瘤
细胞凋亡，然而其诱导胶质瘤细胞凋亡的能力占据主导地位，为其发挥抗胶质瘤效应的主要途径。另外，在LY294002的持续作用
下，部分衰老的肿瘤细胞或许会发生凋亡。这些结论为为临床增强胶质瘤患者的联合化疗奠定了理论基础。 |
| 英文摘要: |
| Objective:PI3K/Akt pathway plays important roles in the initiation and progression of gliomas, and LY294002 is the
specific inhibitor of this pathway. In this study, we mainly investigate the effect of PI3k inhibitor LY294002 on cellular senescence and
apoptosis in U87 human glioma cells to lay a foundation for new therapeutic strategies for glioma patients. Methods: U87 human glioma
cells were divided into control group treated with DMSO and experimental group treated with LY294002 (100uM) in vitro. Using the
methods of beta-SA-Gal staining and flow cytometry, status of cellular senescence and apoptosis were detected and compared.Results: The
senescence index of U87 glioma cells in LY294002 treated group (32.20 ± 4.46%) was significantly higher than that of the DMSO
control group. In addition, comparing with the DMSO control group, expression of the apoptotic protein caspase-3 mRNA was
significantly upregulated in LY294002 treated group (t=8.923, P＜0.05). The apoptosis index of tumor cells in LY294002 treated group
(80.10± 4.832%) was significantly higher than that of the DMSO control group (4.260 ± 1.073%, t=8.923, P＜0.05).Conclusion:LY294002 can not only induce cellular senescence, but also induce apoptosis in tumor cells, while its potential to induce the apoptosis of
glioma cells plays the dominant role, which is the main function to exert its anti-glioma effect. Furthermore, apoptosis might be induced
in part of the senescent tumor cells under the sustained effect of LY294002.2These results laid a theoretical foundation for the clinical
enhancement of the combined chemotherapy in glioma patients. |
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