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Heat Shock Protein 70 Is Induced in Mouse Human Colon Tumor Xenografts After Sublethal Radiofrequency Ablation

From the Department of Surgery, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York.

Correspondence: Address correspondence and reprint requests to: T. S. Ravikumar, MD, Department of Surgery, Albert Einstein College of Medicine/Montefiore Medical Center, 3400 Bainbridge Avenue, 4th Floor, Bronx, NY 10467; Fax: 718-798-1883; E-mail: travikum{at}montefiore.org

Background: Radiofrequency ablation (RFA) destroys tumor cells by generating high temperatures through ionic vibration. Tumor recurrence may be a direct function of sublethal temperature. Further, a set of proteins called heat shock proteins (HSPs) can be synthesized under heat stress to facilitate recovery of tumor cells from heat damage.

Methods: Subcutaneous xenografts were induced in nude mice by injection with HT29 human colon cancer cells. The tumors were exposed surgically and subjected to RFA. The tumors were randomly assigned to achieve a target tumor temperature of 42°C, 45°C, or 50°C. Total RNA and cell lysates were isolated from tumor tissues and subjected to reverse transcription-polymerase chain reaction and Western blot analyses, respectively, at various time points after treatments for assessing HSP expression. For in vitro experiments, HT29 cells were subjected to variable temperatures, and HSP expression was assayed.

Results: During a 50-day follow-up, the recurrence rates were 0% at 50°C, 30% at 45°C, and 100% at 42°C. The messenger RNA and protein levels of HSP90 and HSP27 remained unchanged after RFA at 45°C; however, HSP70 was induced at 4 and 10 hours after RFA. In vitro HT29 culture cells subjected to a heated water bath exhibited a cellular sensitivity to heat and change of HSP expression similar to those in tumor xenografts subjected to RFA.

Conclusions: Our data establish the requisite heat parameters during RFA for human colon tumors in vitro and in vivo. Because HSP70 plays an important role in protecting cell death from a variety of stresses, HSP70 could be a potential target for enhancing the efficacy of RFA.

Key Words: Radiofrequency ablation • Colon cancer • Hyperthermia • Heat shock protein