Aurora kinase a inhibitor MLN8237 suppresses pancreatic cancer growth

Pancreatology. 2022 Jun;22(5):619-625. doi: 10.1016/j.pan.2022.03.019. Epub 2022 Apr 13.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is notorious for high mortality due to limited options of appropriate chemotherapy drugs. Here we report that Aurora kinase-A expression is elevated in both human and mouse PDAC samples. MLN8237, an inhibitor of Aurora kinase-A, efficiently reduced the proliferation and motility of PDAC cells in vitro as well as tumor growth in orthotropic xenograft model and genetic pancreatic cancer animal models (p53/LSL/Pdx-Cre mice) in vivo. MLN8237 exhibited tumor inhibitory effect through inhibiting proliferation and migration, and inducing apoptosis and senescence. These results provide the molecular basis for a novel chemotherapy strategy for PDAC patients.

Keywords: Apoptosis; Aurora kinase; Pancreatic cancer; Senescence; Xenograft.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Aurora Kinase A* / antagonists & inhibitors
  • Aurora Kinase A* / genetics
  • Aurora Kinase A* / metabolism
  • Azepines* / pharmacology
  • Carcinoma, Pancreatic Ductal* / drug therapy
  • Carcinoma, Pancreatic Ductal* / enzymology
  • Carcinoma, Pancreatic Ductal* / genetics
  • Carcinoma, Pancreatic Ductal* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Mice
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / enzymology
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / pathology
  • Protein Kinase Inhibitors / pharmacology
  • Pyrimidines* / pharmacology

Substances

  • Azepines
  • MLN 8237
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Aurora Kinase A