p38β MAP kinase as a therapeutic target for pancreatic cancer

Chem Biol Drug Des. 2012 Aug;80(2):266-73. doi: 10.1111/j.1747-0285.2012.01395.x. Epub 2012 May 23.

Abstract

Pancreatic cancer is very difficult to diagnose in its early stage. Molecular marker and imaging have not proven to be accurate modalities for screening of pancreatic cancer. This study aims to develop p38β as a protein marker for pancreatic cancer and to design peptide inhibitor against the same. The serum p38β level of pancreatic cancer (n = 35; 5.06 μg/mL) was twofold higher compared to that of the chronic pancreatitis (n = 10; 2.92 μg/mL) and matched normal control (n = 10; 2.86 μg/ml) (p < 0.0005). Peptide inhibitors were designed to inhibit the activity of p38β and the kinetic assay had shown the dissociation constant, (K(D)) to be 3.16 × 10(-8) M and IC(50), 25 nM by Surface Plasmon Resonance (SPR) and Enzyme-Linked Immunosorbent Assay (ELISA), respectively. The peptide inhibitor also significantly reduced viability and induced cytotoxicity in Human Pancreatic carcinoma epithelial-like cell line (PANC-1) cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase 11 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 11 / blood
  • Mitogen-Activated Protein Kinase 11 / metabolism
  • Molecular Targeted Therapy
  • Pancreas / cytology
  • Pancreas / drug effects
  • Pancreas / pathology
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / enzymology*
  • Pancreatic Neoplasms / pathology
  • Pancreatitis, Chronic / blood
  • Pancreatitis, Chronic / enzymology
  • Peptides / chemistry*
  • Peptides / pharmacology*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Peptides
  • Mitogen-Activated Protein Kinase 11