Pei Zhe, Fu Wei, Wang Gongping
Section for Gastrointestinal Tumor Surgery, Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan, China.
Section for Gastrointestinal Tumor Surgery, Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan, China.
Biochem Biophys Res Commun. 2017 Nov 4;493(1):455-460. doi: 10.1016/j.bbrc.2017.08.170. Epub 2017 Sep 13.
The pancreatic cancer is among the most aggressive malignancies with strong proclivity to metastasis. The malignancy during pancreatic cancer progression is largely ascribed to epithelial-mesenchymal transition (EMT). Here we showed that toosendanin (TSN), which is an active component in traditional Chinese medicine, can strongly attenuate pancreatic cancer progression. TSN suppressed the viability and grow of pancreatic cancer cells in a dose-dependent manner. The migration and invasion of pancreatic cancer cells were also consistently inhibited dose-dependently. TSN can reverse the TGF-β induced EMT and morphological change in pancreatic cancer cells by increasing Ecadherin expression while reducing Vimentin, ZEB1 and SNAIL levels. Furthermore, TSN evidently repressed xenograft tumor growth in mouse pancreatic cancer models without significantly toxic side effects. Mechanistic studies suggested that TSN mediated pancreatic cancer inhibition by blocking Akt/mTOR signaling pathway. Our results showed that TSN inhibits pancreatic cancer progression via downregulating Akt/mTOR signaling. Since the concentrations of TSN used in current study is very low, our results demonstrated that TSN can inhibit pancreatic cancer progression thereby implying that TSN can be used as a potential pharmacological agent especially in treatment of pancreatic cancer.
胰腺癌是侵袭性最强的恶性肿瘤之一，极易发生转移。胰腺癌进展过程中的恶性程度很大程度上归因于上皮-间质转化（EMT）。在此我们表明，中药中的活性成分川楝素（TSN）能显著减弱胰腺癌的进展。TSN以剂量依赖的方式抑制胰腺癌细胞的活力和生长。胰腺癌细胞的迁移和侵袭也同样呈剂量依赖性受到抑制。TSN可通过增加E-钙黏蛋白表达，同时降低波形蛋白、锌指蛋白E盒结合蛋白1（ZEB1）和锌指转录抑制因子SNAIL的水平，逆转转化生长因子-β（TGF-β）诱导的胰腺癌细胞EMT及形态变化。此外，TSN在小鼠胰腺癌模型中明显抑制异种移植瘤生长，且无明显毒副作用。机制研究表明，TSN通过阻断Akt/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路介导对胰腺癌的抑制作用。我们的结果表明，TSN通过下调Akt/mTOR信号通路抑制胰腺癌进展。由于本研究中使用的TSN浓度非常低，我们的结果表明TSN可抑制胰腺癌进展，这意味着TSN可作为一种潜在的药物制剂，尤其可用于胰腺癌的治疗。
