Effect of Neoadjuvant Chemoradiation Therapy on Proteasome Pool in Rectal Cancer

Bull Exp Biol Med. 2017 Dec;164(2):191-194. doi: 10.1007/s10517-017-3955-z. Epub 2017 Nov 27.

Abstract

In untreated rectal cancer patients, the chymotrypsin-like activity of proteasomes in tumor tissue was 3-fold higher than that in conventionally normal tissue, which is explained by up-regulation of expression of immunoproteasomes and total pool of proteasomes. After neoadjuvant chemoradiation therapy, expressions of the total pool of proteasomes and immunoproteasomes in the tumor as well as the relative ratios of these indices to those in conventionally normal tissue were smaller by 1.4-3.3 times in comparison with the untreated patients. These changes were paralleled with pronounced (4.5-fold) down-regulation of proteasome activity in the tumor and a 3.7-fold decrease of activity ratio for the proteasomes in tumor and in conventionally normal tissue. The number of immunoproteasome subunits and the chymotrypsin-like activity of proteasomes can be viewed as potential markers to prognosticate effectiveness of neoadjuvant chemoradiation therapy in rectal cancer patients.

Keywords: chymotrypsin-like activity of proteasomes; immunoproteasomes; neoadjuvant chemoradiation therapy; rectal cancer.

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Capecitabine / therapeutic use
  • Chemoradiotherapy / methods
  • Cysteine Endopeptidases / genetics*
  • Cysteine Endopeptidases / immunology
  • Gamma Rays / therapeutic use
  • Gene Expression
  • Humans
  • Neoadjuvant Therapy / methods
  • Proteasome Endopeptidase Complex / drug effects
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / immunology
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteasome Endopeptidase Complex / radiation effects
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / surgery
  • Rectal Neoplasms / therapy*

Substances

  • Antineoplastic Agents
  • LMP-2 protein
  • Capecitabine
  • Cysteine Endopeptidases
  • LMP7 protein
  • PSMB10 protein, human
  • Proteasome Endopeptidase Complex