Histone deacetylase inhibitor, 2-propylpentanoic acid, increases the chemosensitivity and radiosensitivity of human glioma cell lines in vitro.

摘要: BACKGROUND Treatment for malignant glioma generally consists of cytoreductive surgery followed by radiotherapy and chemotherapy. In this study, we intended to investigate the effects 2-propylpentanoic acid (VPA), a histone deacetylase inhibitor, on chemosensitivity radiosensitivity in human cell lines. METHODS Human lines, T98-G, SF295, were treated with temozolomide (TMZ) or irradiation (IR), without VPA (1.0 mmol/L). Then, cytotoxicity clonogenic survival assay was performed. Cell cycle stage, apoptosis, autophagy also detected using flow cytometry dansyl monocadaverin (MDC) incorporation assay. One-way analysis variance (ANOVA) t-test used analyze differences among variant groups. RESULTS Mild revealed both T98-G 50% inhibiting concentration (IC50) value (3.85 ± 0.58) mmol/L (2.15 0.38) mmol/L, respectively; while IC50 TMZ (0.20 0.09) (0.08 0.02) SF295. Moreover, if combined mmol/L) 96 hours, sensitivity cells significant increased (P < 0.05). The surviving fractions at 2 Gy (SF2) SF295 exposed IR alone 0.52 0.58. However, when IR, SF2 dropped 0.39 = 0.047) 0.49 0.049), respectively. plus resulted decrease proportion G2 phase apoptotic rates as well lines 0.01). CONCLUSION may enhance activities possibly through block promote autophagy, thus could be potential sensitizer treatment.