Histone deacetylase inhibitor, 2-propylpentanoic acid, increases the chemosensitivity and radiosensitivity of human glioma cell lines in vitro / 中华医学杂志(英文版)

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

A method of acutely isolating rat dorsal root ganglion neurons for patch-clamp study of single-channel / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To establish a method of acutely isolating dorsal root ganglion (DRG) neurons for patch clamp study of single-channel.</p><p><b>METHODS</b>DRG neurons of rats were acutely isolated by enzymatic digestion and mechanical blowing.</p><p><b>RESULTS</b>The acutely isolated DRG cells were easy to form the higher sealing resistance (> 5G Omega), which lowered noise level, so that pA-level single channel currents could be recorded.</p><p><b>CONCLUSION</b>The acutely isolated DRG neurons in this study are an ideal for patch-clamp study of single-channel.</p>

Correlation of DNA-PK activity with anti-cancer drug-sensitivity in human gliomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship between DNA-dependent protein kinase (DNA-PK) activity and anti-cancer drug sensitivity in human glioma tissues.</p><p><b>METHODS</b>Human glioma specimens were primarily cultured and its sensitivity to several anti-cancer drugs were evaluated by MTT assay. Nuclear protein was extracted from the glioma sample of the same patient and its DNA-PK activity was determined by a biotinylated DNA-PK assay with p53-derived peptide as a specific substrate.</p><p><b>RESULTS</b>DNA-PK activity varied widely among these glioma samples. Of all 36 samples, 16 showed higher DNA-PK activity (relative activity > or = 0.40) and 20 samples with lower DNA-PK activity (relative activity < 0.40). The gliomas sensitive to DDP and VCR as evaluated by inhibition rate (IR > or = 50%) under plasma peak concentration (PPC) showed lower DNA-PK activity than the resistant ones (IR < 50%) (t = -3.445, P < 0.01). Furthermore, the gliomas with higher DNA-PK activity showed lower inhibition rate (IR < 50%) than those with lower DNA-PK activity ones (t = -2.145, P < 0.05).</p><p><b>CONCLUSION</b>DNA-PK activity is significantly associated with anti-cancer drug sensitivity to DDP and VCR in human gliomas. DNA-PK activity could be used as a new biomarker for the chemotherapy sensitivity of human gliomas.</p>