RT Journal Article
SR Electronic
T1 Sodium Valproate, a Histone Deacetylase Inhibitor, Enhances the Efficacy of Vinorelbine-Cisplatin-based Chemoradiation in Non-small Cell Lung Cancer Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 6565
OP 6572
VO 34
IS 11
A1 VLADIMIR GAVRILOV
A1 KONSTANTIN LAVRENKOV
A1 SAMUEL ARIAD
A1 SHRAGA SHANY
YR 2014
UL http://ar.iiarjournals.org/content/34/11/6565.abstract
AB Aim: To enhance the anticancer activity of vinorelbine, cisplatin and ionizing radiation (IR) combination against non-small cell lung cancer (NSCLC) cells by co-administration of sodium valproate (VPA), a histone deacetylase inhibitor, and to elucidate molecular events underpinning treatment efficacy. Materials and Methods: The NSCLC A549 cell line was treated with cisplatin (0.2 μg/ml), vinorelbine (2 nM), VPA (1 mM) and IR (2.5 Gy) alone, or in combination. Cell proliferation, cell-cycle distribution, apoptosis, and levels of DNA double-strand breaks, activated DNA damage checkpoint kinases pCHK1, pCHK2, cell-cycle inhibitors p21CIP1/WAF1 and p27KIP1 were assessed. Results: VPA markedly enhanced the DNA-damaging effect of the cisplatin-vinorelbine-IR combination and induced increased DSBs, and expression of pCHK2, pCHK1, p21CIP1/WAF1 and p27KIP1. These molecular changes led to cell-cycle arrest and increased apoptosis and consequently markedly curtailed cancer cell growth. Conclusion: VPA markedly enhances the anticancer activity of cisplatin-vinorelbine-IR combination. This finding has translational implications for enhancing the efficacy of anticancer treatment and for reducing side-effects by reducing doses of radiation and drugs.