Wang Dan, Xin Yan, Tian Yanqiu, Li Wenhui, Sun Dan, Yang Yi
Department of Gastrointestinal Tumor Pathology of Cancer Institute and General Surgery Institute, The First Hospital of China Medical University, Shenyang, China; Colledge of Pharmacy, Liaoning University, Shenyang, China.
Department of Gastrointestinal Tumor Pathology of Cancer Institute and General Surgery Institute, The First Hospital of China Medical University, Shenyang, China.
Exp Cell Res. 2017 Mar 1;352(1):34-44. doi: 10.1016/j.yexcr.2017.01.012. Epub 2017 Jan 26.
Pseudolaric acid B (PAB) is the major bioactive constituent in the root bark of Pseudolarix kaempferi and has been reported to have cytotoxicity against tumor cells. Our in vivo experiments showed that PAB could inhibit gastric cancer cell lung metastasis in a nude mouse haematogenous dissemination model. To evaluate the anti-metastasis mechanism of PAB in gastric cancer cells, cytological experiments were performed. The results showed that PAB could inhibit the adhesion ability to matrigel, migration, invasion and colony formation ability of BGC-823 and MKN-45 cells. Western blot further confirmed that the inhibitory effects of PAB on anti-metastasis may involve regulating the expression of the metastasis-related proteins MMP-9, HIF-1α, VEGF, VEGFR2, E-Cadherin and Ezrin. We obtained further proof that PAB which could be used as a multi-targeted agent to inhibit the PI3K/AKT, ERK1/2 and mitochondria-mediated apoptosis pathways and consequently suppress tumor growth and metastasis. Our experiments suggest that PAB-induced effects may have novel therapeutic applications for the treatment of gastric cancer.
土荆皮酸B（PAB）是金钱松根皮中的主要生物活性成分，据报道对肿瘤细胞具有细胞毒性。我们的体内实验表明，PAB在裸鼠血行播散模型中可抑制胃癌细胞的肺转移。为了评估PAB在胃癌细胞中的抗转移机制，我们进行了细胞学实验。结果表明，PAB可抑制BGC-823和MKN-45细胞对基质胶的黏附能力、迁移、侵袭和集落形成能力。蛋白质免疫印迹法进一步证实，PAB对抗转移的抑制作用可能涉及调节转移相关蛋白MMP-9、HIF-1α、VEGF、VEGFR2、E-钙黏蛋白和埃兹蛋白的表达。我们进一步证明，PAB可作为一种多靶点药物，抑制PI3K/AKT、ERK1/2和线粒体介导的凋亡途径，从而抑制肿瘤生长和转移。我们的实验表明，PAB诱导的效应可能对胃癌治疗具有新的治疗应用。
