Research Paper Volume 13, Issue 22 pp 24753—24767

Fisetin inhibits the proliferation, migration and invasion of pancreatic cancer by targeting PI3K/AKT/mTOR signaling

Yanyi Xiao1, *, , Yilong Liu2, *, , Zhiwei Gao3, *, , Xian Li2, , Min Weng1, , Chenghao Shi1, , Cheng Wang1, , Linxiao Sun1, ,

  • 1 Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Medical University First Affiliated Hospital, Wenzhou 325015, Zhejiang, China
  • 2 Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology, The State Agriculture Ministry Laboratory of Horticultural Plant Growth, Development and Quality Improvement, Zhejiang University, Hangzhou 310058, Zhejiang, China
  • 3 School of Medicine, The Second Affiliated Hospital of Zhejiang University, Hangzhou 310009, Zhejiang, China
* Equal contribution

Received: March 22, 2021       Accepted: November 11, 2021       Published: November 25, 2021      

https://doi.org/10.18632/aging.203713
How to Cite

Copyright: © 2021 Xiao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Pancreatic cancer is an extremely malignant digestive tract tumor. With the increase of chemotherapeutic resistance of pancreatic cancer, clinical treatment is in a dilemma. Hence, it is pivotal to design an effective drug for treating individuals with pancreatic cancer. Fisetin extracted from vegetables, as well as fruits was explored to possess antioxidant, anti-cancer, anti-inflammatory along with anti-microbial properties. Nonetheless, there is limited research focusing on the utility of fisetin as an inhibitor of pancreatic cancer. Similarly, the mechanism through which Fisetin dampens pancreatic cancer remains unknown. This research work systematically evaluated the possible anti-cancer influences of fisetin in pancreatic cancer, as well as explored its responsible molecular mechanism. Our data revealed that fisetin obviously dampens pancreatic cancer progress in vitro along with in vivo dose-dependently. Furthermore, we established that fisetin repressed pancreatic cancer via explicitly targeting PI3K/AKT/mTOR signaling cascade and not the JAK2 cascade. Our data clarified that fisetin is a prospective anti-cancer drug for pancreatic cancer, as well as indicated the distinct molecular target of fisetin.

Abbreviations

AKT: protein kinase B; CCK-8: Cell Counting Kit-8; ECM: extracellular matrix; EMT: Epithelial-mesenchymal transition; FBS: fetal bovine serum; JAK2: Janus kinase 2; MMP-2: matrix matalloproteinases 2; MMP-9: matrix matalloproteinases 9; mTOR: mammalian target of rapamycin; PBS: phosphate buffer saline; PC: pancreatic cancer; PI3K: phosphatidylinositol 3 kinase.