In Vitro and In Vivo Radiosensitizing Effect of Valproic Acid on Fractionated Irradiation.
- Author:
Eui Kyu CHIE
1
;
Jin Hee SHIN
;
Jin Ho KIM
;
Hak Jae KIM
;
In Ah KIM
;
Il Han KIM
Author Information
- Publication Type:In Vitro ; Original Article
- Keywords: Radiation tolerance; Valproic acid; Radiation; Glioblastoma; Non-small-cell lung carcinoma
- MeSH: Animals; Carcinoma, Non-Small-Cell Lung; Cell Line; Glioblastoma; Histone Deacetylase Inhibitors; Mice; Radiation Tolerance; Radiation-Sensitizing Agents*; Radiotherapy; Valproic Acid*
- From:Cancer Research and Treatment 2015;47(3):527-533
- CountryRepublic of Korea
- Language:English
- 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.
