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In Vitro and In Vivo Radiosensitizing Effect of Valproic Acid on Fractionated Irradiation

Authors :
Eui Kyu Chie
In Ah Kim
Il Han Kim
Jin Hee Shin
Hak Jae Kim
Jin Ho Kim
Source :
Cancer Research and Treatment. 47:527-533
Publication Year :
2014
Publisher :
Korean Cancer Association, 2014.

Abstract

PURPOSE This study was conducted in order to validate the radiosensitization effect of valproic acid, a biologically available histone deacetylase inhibitor, for fractionated radiation. MATERIALS AND METHODS Radiosensitization effect of valproic acid was tested for the A549 cell line and U87MG cell line in vitro. Fractionated irradiation of 12 Gy in four fractions was administered on D2-5 with valproic acid, 150 mg/Kg, ip, bid for six consecutive days (D1-6) to A549 and U87MG tumors implanted in BALB/c-nude mice. A growth delay curve was formulated. RESULTS Radiosensitization effect of valproic acid was found for both cell lines; A549 at 1.5 mM and 3.0 mM concentration and U87MG at 3.0 mM concentration. In growth delay analysis, a statistically significant radiosensitization effect was observed for both tumors (p < 0.001 for both tumors). Difference for change in slope for control and valproic acid versus radiotherapy and radiotherapy plus valproic acid showed borderline significance for the U87MG cell line (p=0.065), indicating beyond additive effect, whereas this difference was statistically insignificant for A549 tumor (p=0.951), indicating additive effect. CONCLUSION Results of this study indicate that a radiosensitizing effect for fractionated radiotherapy of valproic acid for A549 and U87MG tumors in vivo is evident and that it may be more than additive for U87MG tumors. Further exploitation of histone deacetylase inhibitors in clinical trials is warranted.

Details

ISSN :
20059256 and 15982998
Volume :
47
Database :
OpenAIRE
Journal :
Cancer Research and Treatment
Accession number :
edsair.doi...........d35326e65fbd7b9bf8dd0f73f8f5ffef
Full Text :
https://doi.org/10.4143/crt.2014.026