摘要
目的 探讨全反式维甲酸(ATRA)对腺病毒为载体的单纯疱疹病毒胸苷激酶(Ad-TK)/N氧鸟苷(GCV)治疗激素非依赖性前列腺癌旁观者效应的影响及其机理。方法 采用免疫细胞化学和Western blot方法检测ATRA作用前后前列腺癌细胞株PC-3表达连接蛋白(Cx)43的水平和位置,应用MTT法检测细胞存活率,观察ATRA处理前后Ad—TK/GCV系统治疗PC-3细胞旁观者效应的变化。结果 PC-3细胞弱表达Cx43,总体表达率为27.7%;在浓度〉1×10^-6mol/L的ATRA作用下,Cx43水平表达阳性率达75.7%,以胞膜表达为主,明显高于ATRA处理前(P〈0.05)。在达到明显旁观者效应(细胞生存率50%)时,Ad—TK/GCV系统组需要TK^+PC-3细胞数为50%,而ATRA联合Ad—TK/GCV系统组需要TK^+PC-3细胞数仅为30%,二者比较差异有统计学意义(P〈0.05)。结论 前列腺癌Ad—TK/GCV治疗的旁观者效应与Cx43表达及定位有关,AT—RA可以通过提高Cx43的表达增强旁观者效应。
Objective To investigate the bystander effect of all-trans retinoic acid on the recombinant of adenovirus and herpes simplex virus thymidine kinase(Ad-TK)/ganciclover(GCV) system in the treatment of androgen-unresponsive prostate cancer cell line. Methods Immunocytochemistry and Western blot were used to analyze the expression and location of Connexin(Cx)43 in PC-3 cells before and after treatment with ATRA; meanwhile, the bystander-effect of Ad-TK/GCV against PC-3 cells was determined by the cells growth inhibitory rate with methyl thiazolyl tetrazolium(MTT). Results The expression of Cx43 was low (27.7%) in PC-3 cells, but increased (75.7%) and located mainly on the membrane after treatment with ATRA (over 10^-6 mol/L). Compared with using AdTK/GCV system only, ATRA could augment significantly the bystander effect of Ad-TK/GCV system which was showed by reducing the ratio of TK positive PC-3 cells from 50% to 30%(P〈0.05). Conclusions In the treatment of prostate cancer, there is relationship between Cx43 expression and location and Ad-TK/GCV bystander effect. ATRA could up-regulate the expression of Cx43 and thereby enhance the bystander effect.
出处
《中华泌尿外科杂志》
CAS
CSCD
北大核心
2007年第4期274-276,共3页
Chinese Journal of Urology
基金
江苏省科技发展计划基金资助项目(BS2003013)
关键词
前列腺肿瘤
癌
维甲酸
旁观者效应
Prostatic neoplasms
Carcinoma
Retinoic acid
Bystander effect