Notch1 and PI3K/Akt signaling blockers DAPT and LY294002 coordinately inhibit metastasis of gastric cancer through mutual enhancement

  • Xingchun Peng
  • Jianrui Zhou
  • Bin Li
  • Tao Zhang
  • Yamin Zuo
  • Xinsheng GuEmail author
Original Article



Blockade of either Notch1 or PI3K/Akt pathway inhibits metastasis of gastric cancer. However, whether blockade of both pathways coordinately exerts such an effect remains unknown. In this study, we aimed to investigate the effects of combined treatment with Notch1 signaling blocker DAPT and PI3K/Akt signal blocker LY294002 on metastasis of gastric cancer.


Notch intracellular domain (NICD) and phosphorylated Akt (p-Akt) levels in gastric cancer tissues and their adjacent normal tissue samples and gastric cancer SGC7901 and AGS cells and normal GES-1 cells were determined using immunohistochemistry and Western blotting. The effects of combined DAPT and LY294002 on metastasis of gastric cancer were evaluated by examining migration and invasion potential of SGC7901 cells using wound healing and transwell assays, determining changes in the levels of epithelial–mesenchymal transition biomarkers and MMP-9, Notch1, HES1, and phosphorylation of Akt in gastric cancer SGC7901 cells and/or AGS cells in vitro using Western blotting, and metastasis of gastric cancer to lungs in BALB/c nude mice after treatment.


NICD and p-Akt levels were significantly higher in gastric cancer tissues and SGC7901 and AGS cells than those in the normal control and GES-1 cells. Migration and invasion potential of SGC7901 cells, EMT biomarkers and MMP-9 in SGC7901 cells, and metastasis of gastric cancer to lungs in mice were coordinately inhibited by DAPT and LY294002. In addition, DAPT and LY294002 coordinately inhibited the levels of Notch1, HES1, and p-Akt in gastric cancer cells.


DAPT and LY294002 coordinately inhibited metastasis of gastric cancer through mutual enhancement.


Gastric cancer Notch1 PI3K/Akt Metastasis 


Author contributions

XP, JZ, and BL collected and analyzed data. TZ and YZ collected data. XP and XG conceived the study and wrote the manuscript.


This work was supported by the Department of Education of Hubei Province (Grant No. B2018109), Natural Science Foundation of Hubei Province of China (2016CFB530), Faculty Development Foundation of Hubei University of Medicine (2014QDJZR01), and Department of Health of Xuhui District of Shanghai (SHXH201402).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.College of Basic Medical SciencesHubei University of MedicineShiyanChina
  2. 2.Department of Rehabilitation Medicine, Taihe HospitalHubei University of MedicineShiyanChina
  3. 3.Department of Pathology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Shanghai Clinical CenterFudan University, CASShanghaiChina
  4. 4.Department of Neurosurgery, Taihe HospitalHubei University of MedicineShiyanChina

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