摘要
目的 观察芹黄素 (apigenin)对前列腺癌 (PC)细胞PC 3m生长的影响及其对单纯疱疹胸苷激酶 /更昔洛韦 (HSV tk/GCV)系统“旁观者效应”的调控 ,寻求增强该系统对PCa疗效的途径。方法 四甲基偶氮唑盐比色法 (MTT法 )检测 1、10、10 0 μmol/Lapigenin对PC 3m细胞生长的影响 ,观察 10 μmol/Lapigenin预处理后GCV对tk基因阳性 (tk+ )比例为 10 %和 5 %的混合细胞的杀伤作用及 18 α 甘草次酸 ( 18 α glycyrrhetinicacidAGA)对其影响 ,并检测apigenin联合GCV的杀伤效应。结果 Apigenin可抑制PCa细胞增殖 ,呈时间和剂量依赖关系 (P <0 .0 5 0 ) ;低浓度( 10 μmol/L) apigenin预处理对PC 3m细胞增殖无影响但可使“旁观者效应”明显增强 (P <0 .0 0 1) ,10 μmol/L和 10 0 μmol/LGCV对tk+ 为 10 %细胞的杀伤率由 ( 16.15± 1.64 ) %和 ( 2 3 .46± 3 .2 1) %提高到 ( 4 5 .89± 3 .2 8) %和 ( 5 9.86± 2 .44 ) % ,该作用可被AGA抵消。联合应用apigenin和GCV后杀伤率更为显著 ,达 ( 62 .5 8± 4.2 9) %和 ( 83 .16± 3 .72 ) %。结论 Apigenin不仅可以直接杀伤PC细胞 ,还可通过增强HSV tk/GCV系统“旁观者效应” ,发挥间接杀瘤效应 ,从而提高该系统治疗PC疗效。
Objective To observe the influence of apigenin on the proliferation of a prostate caner (PCa) cell line named PC-3m and to evaluate the modulation of apigenin on the so called “bystander effect” induced by herpes simplex virus-thymidine kinase/ganciclovir (HSV-tk/GCV) system.Methods The role of apigenin (1,10,100 μmol/L) on the growth of PC-3m cells weas assessed by MTT assay.After apigenin pretreated,the killing effect of GCV on the mixture cells with ratio of 10% and 5% tk gene transfected (tk+) cells was determined,and the impact of 18-α-glycyrrhetinic acid (AGA) on the procedure was evaluated.Furthermore,the cooperative therapeutic index of apigenin combined with GCV was estimated as well.Results Apigenin could inhibit the growth-of PCa cells in a time- and dose-dependent manner (P<0.050～0.001).The extent of bystander effect was obviously improved by pretreatment with 10μmol/L apigenin,and the cytotoxicity of 10 μmol/L and 100 μmol/L GCV on 10 % tk+ PC-3m cells were raised from (16.15±1.64) % and (23.46±3.21) % to (45.89±3.28) % and (59.86±2.44) % respectively.The effect evoked by apigenin abolished when co-culture with 18-α-glycyrrhetinic acid (AGA).It was demonstrated that the collaboration of apigenin and GCV resulted in statistically significant enhanced therapeutic index in which cytotoxicity was (62.58±4.29) % and (83.16±3.72) %,respectively.Conclusion Apigenin could exert dual antineoplastic functions through reinforcing bystander effect and suppressing malignant prostate cells directly,and it is strongly indicated that such a cooperative strategy provides a brand-new valid modality for PCa treatment.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2003年第11期1023-1024,共2页
Chinese Journal of Experimental Surgery
