Heat shock protein 70 is induced in mouse human colon tumor xenografts after sublethal radiofrequency ablation.

Abstract:

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 degrees C, 45 degrees C, or 50 degrees 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 degrees C, 30% at 45 degrees C, and 100% at 42 degrees C. The messenger RNA and protein levels of HSP90 and HSP27 remained unchanged after RFA at 45 degrees 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.

journal_name

Ann Surg Oncol

authors

Yang WL,Nair DG,Makizumi R,Gallos G,Ye X,Sharma RR,Ravikumar TS

doi

10.1245/ASO.2004.08.013

keywords:

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

399-406

issue

4

eissn

1068-9265

issn

1534-4681

pii

11/4/399

journal_volume

11

pub_type

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