2′-羟基黄烷酮对前列腺癌细胞的放射增敏作用及机制探讨

目的 研究2′-羟基黄烷酮(2′-HF)对前列腺癌细胞的放射增敏作用并初步探讨其机制。方法 应用克隆形成实验、叔丁基过氧化氢(TBHP)氧化损伤实验、Hoechst荧光染色、Annexin V-FITC和PI流式细胞仪凋亡检测实验检测2′-HF对前列腺癌VCaP细胞的放射敏感性影响。应用Western blot方法检测2′-HF对VCaP细胞中AKT、p-AKT、AKR1C3蛋白表达水平影响并初步探讨作用机制。采用t检验和析因方差分析检验结果。结果 克隆形成实验结果提示经2′-HF处理的VCaP细胞在照射后增殖能力明显低于空白对照组(P=0.010),SR=1.19;TBHP氧化损伤实验结果提示经2′-HF处理的VCaP细胞的抗氧化损伤能力明显弱于空白对照组(P=0.015);Hoechst荧光染色、Annexin V-FITC和PI流式凋亡检测实验结果提示2′-HF联合放射线会增加VCaP细胞调亡(P=0.001);Western blot实验结果提示2′-HF可以抑制VCaP细胞中p-AKT、AKR1C3蛋白的表达(P=0.013,P=0.016)。结论 2′-HF可提高前列腺癌细胞的放射敏感性,这可能与其对前列腺癌细胞中AKT通路阻滞或AKR1C3蛋白表达抑制相关。

Radiosensitizing effect and mechanism of 2'-hydroxyflavanone in prostate cancer cells

Objective To study the radiosensitizing effect of 2'-hydroxyflavanone (2'-HF) on prostate cancer cells,and to preliminarily investigate its mechanism.Methods Colony formation assay,tert-butylhydroperoxide (TBHP) oxidative stress assay,Hoechst staining,and apoptosis flow cytometry using Annexin V-FITC and propidium iodide (PI) were performed to measure the impact of 2'-HF on the radiosensitivity of VCaP prostate cancer cells.Western blot was used to determine the effects of 2'-HF on expression of AKT,phosphorylated AKT (p-AKT),and aldo-keto reductase 1 C3 (AKR1 C3) in VCaP cells and preliminarily investigate the mechanism.Data were analyzed by t test and factorial analysis of variance.Results The results of colony formation assay indicated that after exposure to radiation,VCaP cells treated with 2'-HF had a significantly lower proliferation level than cells in the control group (P=0.010),yielding a sensitization enhancement ratio of 1.19.The resuhs of TBHP oxidative stress assay suggested that VCaP cells treated with 2'-HF had significantly weaker anti-oxidative capacity than cells in the control group (P=0.015).Hoechst staining and apoptosis flow cytometry with Annexin V-FITC and PI indicated that 2'-HF treatment plus irradiation significantly enhanced apoptosis in VCaP cells (P=0.001.The results of Western blot suggested that 2'-HF treatment significantly inhibited the protein expression of p-AKT and AKR1C3 in VCaP cells (P=0.013 and P=0.016).Conclusions 2'-HF can enhance the radiosensitivity of prostate cancer cells,which is probably associated with its inhibitory effects on AKT pathway and AKR1C3 expression in prostate cancer cells.