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Open Access 01-12-2012 | Research

Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma

Authors: Marie Grøn Saelen, Anne Hansen Ree, Alexandr Kristian, Karianne Giller Fleten, Torbjørn Furre, Helga Helseth Hektoen, Kjersti Flatmark

Published in: Radiation Oncology | Issue 1/2012

Abstract

Background

The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC). Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT) is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials.

Methods

Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models.

Results

Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth.

Conclusions

Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials.

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Title: Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma
Authors: Marie Grøn Saelen
Anne Hansen Ree
Alexandr Kristian
Karianne Giller Fleten
Torbjørn Furre
Helga Helseth Hektoen
Kjersti Flatmark
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Radiation Oncology / Issue 1/2012
Electronic ISSN: 1748-717X
DOI: https://doi.org/10.1186/1748-717X-7-165

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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