Laboratory/Clinical Translational Research

Proteasome Inhibition Potentiates the Cytotoxic Effects of Hyperthermia in HT-29 Colon Cancer Cells through Inhibition of Heat Shock Protein 27
Fei Chen, Reza Rezavi, Cha-Chi Wang, Lawrence E. Harrison

Division of Surgical Oncology, UMDNJ - New Jersey Medical School, Newark, N.J., USA

Address of Corresponding Author

Oncology 2007;73:98-103 (DOI: 10.1159/000120997)

  Key Words

• Hyperthermia
• Heat shock
• Colon cancer

  Abstract

Background: The purpose of this study was to investigate whether proteasome inhibition acts as a thermal sensitizing agent to induce tumor cell death in a colon cancer cell line. Methods: HT-29 colon cancer cells were exposed to hyperthermia (43°C) in the presence of proteasome inhibition for 1 h. Viable cell mass and apoptosis were measured by MTT and annexin V staining, respectively. Protein levels were determined by Western blot analysis. Results: A significant synergistic effect on cell viability with proteasome inhibition was noted under hyperthermic conditions compared to hyperthermia alone (p < 0.05). Increases in phosphorylated ERK and decreases in HSP27 levels were observed in the cells exposed to proteasome inhibition at 43°C. Pretreatment with an inhibitor of ERK yielded an additional increase in apoptosis when used in combination with proteasome inhibition and hyperthermia. Decreased expression of HSP27 by siRNA also resulted in increased thermally induced apoptotic cell death. Conclusions: Thermal sensitization through proteasome inhibition may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Lawrence E. Harrison, MD
Department of Surgery, Division of Surgical Oncology
UMDNJ - New Jersey Medical School
185 South Orange Avenue, MSB G524, Newark, NJ 07103 (USA)
Tel. +1 973 972 5583, Fax +1 973 972 3730, E-Mail L.Harrison@UMDNJ.edu

  Article Information

Received: August 15, 2007
Accepted: August 16, 2007
Published online: March 13, 2008
Number of Print Pages : 6
Number of Figures : 5, Number of Tables : 0, Number of References : 15