糖原合成酶激酶-3β调节人类神经胶质瘤细胞中的肿瘤生长和血管生成。
GSK-3β regulates tumor growth and angiogenesis in human glioma cells.
作者信息
Zhao Peng, Li Qi, Shi Zhumei, Li Charlie, Wang Lin, Liu Xue, Jiang Chengfei, Qian Xu, You Yongping, Liu Ning, Liu Ling-Zhi, Ding Lianshu, Jiang Bing-Hua
机构信息
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
State Key Lab of Reproductive Medicine, Department of Pathology and Collaborative Innovation Center for Cancer Personalized Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China.
出版信息
Oncotarget. 2015 Oct 13;6(31):31901-15. doi: 10.18632/oncotarget.5043.
BACKGROUND
Glioma accounts for the majority of primary malignant brain tumors in adults.
METHODS
Glioma specimens and normal brain tissues were analyzed for the expression levels of GSK-3β and p-GSK-3β (Ser9) by tissue microarray analysis (TMA) and Western blotting. Glioma cells over-expressing GSK-3β were used to analyze biological functions both in vitro and in vivo.
RESULTS
The levels of p-GSK-3β (Ser9), but not total GSK-3β, are significantly up-regulated in glioma tissues compared to normal tissues, and are significantly correlated with the glioma grades. Ectopic expression of GSK-3β decreased the phosphorylation levels of mTOR and p70S6K1; and inhibited β-catenin, HIF-1α and VEGF expression. Forced expression of GSK-3β in glioma cells significantly inhibited both tumor growth and angiogenesis in vivo.
CONCLUSIONS
These results reveal that GSK-3β regulates mTOR/p70S6K1 signaling pathway and inhibits glioma progression in vivo; its inactivation via p-GSK-3β (Ser9) is associated with glioma development, which is new mechanism that may be helpful in developing GSK-3β-based treatment of glioma in the future.
背景
神经胶质瘤占成人原发性恶性脑肿瘤的大多数。
方法
通过组织芯片分析（TMA）和蛋白质免疫印迹法分析神经胶质瘤标本和正常脑组织中GSK-3β和p-GSK-3β（Ser9）的表达水平。使用过表达GSK-3β的神经胶质瘤细胞在体外和体内分析生物学功能。
结果
与正常组织相比，神经胶质瘤组织中p-GSK-3β（Ser9）的水平显著上调，而总GSK-3β的水平未上调，且与神经胶质瘤分级显著相关。GSK-3β的异位表达降低了mTOR和p70S6K1的磷酸化水平；并抑制β-连环蛋白、HIF-1α和VEGF的表达。在神经胶质瘤细胞中强制表达GSK-3β可显著抑制体内肿瘤生长和血管生成。
结论
这些结果表明，GSK-3β调节mTOR/p70S6K1信号通路并在体内抑制神经胶质瘤进展；其通过p-GSK-3β（Ser9）的失活与神经胶质瘤的发展相关，这是一种新机制，可能有助于未来开发基于GSK-3β的神经胶质瘤治疗方法。
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