Embryo Engineering Key Laboratory of Jilin Province, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin 130062, PR China.
Mol Med Rep. 2012 Mar;5(3):788-92. doi: 10.3892/mmr.2011.694. Epub 2011 Dec 6.
The Akt pathway is considered a pivotal player in regulating cell survival, growth, migration and angiogenesis. Disruption of normal Akt/PKB/PTEN signaling frequently occurs in numerous types of human cancers. Therefore, this signaling pathway is regarded as an important target for effective cancer therapeutic strategies. In the present study, methanol extracts from Scutellaria barbata (S. barbata) were determined to be Akt/protein kinase B inhibitory, after screening a panel of 40 traditional Chinese herbs with the Fast Activated Cell-based ELISA (FACE) assay. S. barbata extracts were found to suppress the phosphorylation levels of Akt. This inhibition was Akt kinase-specific as it had no effect on PI3K, the upstream kinase of Akt, whereas the levels of phosphorylated Bad and FHKR, the two downstream targets of Akt, changed as the levels of Akt changed. S. barbata extracts also exhibited cytotoxicity against LoVo and human umbilical vein endothelial cells (HUVECs). Furthermore, this extract inhibited the process of in vitro angiogenesis of HUVECs on Matrigel. S. barbata may be a suitable alternative source with which to isolate small molecules for use as Akt kinase inhibitors.
Akt 通路被认为在调节细胞存活、生长、迁移和血管生成中起着关键作用。在许多类型的人类癌症中，正常的 Akt/PKB/PTEN 信号经常被破坏。因此，这条信号通路被认为是癌症治疗策略的一个重要靶点。在本研究中，通过使用快速激活细胞基于 ELISA（FACE）测定法筛选 40 种中草药，发现黄芩甲醇提取物具有 Akt/蛋白激酶 B 抑制作用。黄芩提取物被发现可抑制 Akt 的磷酸化水平。这种抑制是 Akt 激酶特异性的，因为它对 Akt 的上游激酶 PI3K 没有影响，而 Akt 的两个下游靶点磷酸化 Bad 和 FHKR 的水平则随着 Akt 水平的变化而变化。黄芩提取物还对 LoVo 和人脐静脉内皮细胞（HUVEC）表现出细胞毒性。此外，该提取物抑制了 HUVEC 在 Matrigel 上的体外血管生成过程。黄芩可能是一种合适的替代来源，可以从中分离出小分子作为 Akt 激酶抑制剂。
