Thermal sensitization using induced oxidative stress decreases tumor growth in an in vivo model of hyperthermic intraperitoneal perfusion.

Abstract

The purpose of this study was to extend our in vitro observations that induced oxidative stress under hyperthermic conditions decreases tumor cell growth into a preclinical murine model of hyperthermic perfusion. A nude mouse model of colon cancer carcinomatosis with HT-29-Luc-D6 colon cancer cells was established, and tumor growth was measured by serial bioluminescent imaging. By means of a survival model of hyperthermic perfusion, we demonstrated that perfusion with normothermic saline decreased tumor growth compared with no perfusion controls, and tumor growth was further decreased with hyperthermic perfusion alone. The induction of oxidative stress with hydrogen peroxide in the perfusate at concentrations as high as 600 microM was well tolerated in this model of hyperthermic perfusion. Importantly, induced oxidative stress using hydrogen peroxide under hyperthermic conditions significantly decreased in vivo tumor cell growth compared with all other controls. On the basis of our observations, thermal sensitization through modulation of cellular oxidative stress may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.