CAJ | 학술논문

目的研究甲基转移酶抑制剂5-氮-2-脱氧胞苷(5-Aza-dc)对雄激素依赖性前列腺癌细胞株(LNCaP)生长的抑制作用及对谷胱苷肽-S-转移酶1(GSTP1)和维A酸受体β2(RARβ2)基因甲基化状态的影响. 方法 5-Aza-dc作用LNCaP细胞,观察其生长状态,并应用CCK8法检测5-Aza-dc作用前后LNCaP存活率.巢式甲基化特异性聚合酶链反应方法分析用药后LNCaP的GSTP1和RARβ2基因启动子区5 ’端CpG岛甲基化状态. 结果 5-Aza-dc抑制LNCaP的生长、增殖,作用LNCaP后,其GSTP1和RARβ2基因的甲基化状态出现逆转,以上作用与药物浓度及药物作用时间在一定范围内呈正相关,结果显示小剂量(＜1.0 μmol/L)的5-Aza-dc作用48 h内对细胞有抑制作用,作用72 h后有刺激细胞增长的作用;同样,小剂量的5-Aza-dc作用72 h的细胞GSTP1、RARβ2基因甲基化状态较药物作用48 h未见明显减弱,即应用相对低浓度药物,作用时间超过48 h后其去甲基化效用并无明显增加. 结论 5-Aza-dc能较好抑制LNCaP的生长增殖并有效地逆转DNA的异常甲基化,低浓度药物应用时其作用的持续性和稳定性有所改变,为临床治疗方案的选择提供一定的研究基础.
목적 연구갑기전이매억제제5-담-2-탈양포감(5-Aza-dc)대웅격소의뢰성전렬선암세포주(LNCaP)생장적억제작용급대곡광감태-S-전이매1(GSTP1)화유A산수체β2(RARβ2)기인갑기화상태적영향. 방법 5-Aza-dc작용LNCaP세포,관찰기생장상태,병응용CCK8법검측5-Aza-dc작용전후LNCaP존활솔.소식갑기화특이성취합매련반응방법분석용약후LNCaP적GSTP1화RARβ2기인계동자구5 ’단CpG도갑기화상태. 결과 5-Aza-dc억제LNCaP적생장、증식,작용LNCaP후,기GSTP1화RARβ2기인적갑기화상태출현역전,이상작용여약물농도급약물작용시간재일정범위내정정상관,결과현시소제량(＜1.0 μmol/L)적5-Aza-dc작용48 h내대세포유억제작용,작용72 h후유자격세포증장적작용;동양,소제량적5-Aza-dc작용72 h적세포GSTP1、RARβ2기인갑기화상태교약물작용48 h미견명현감약,즉응용상대저농도약물,작용시간초과48 h후기거갑기화효용병무명현증가. 결론 5-Aza-dc능교호억제LNCaP적생장증식병유효지역전DNA적이상갑기화,저농도약물응용시기작용적지속성화은정성유소개변,위림상치료방안적선택제공일정적연구기출.
Objective To investigate the effects of 5-Aza-2'-deoxycytidine (5-Aza-dc),a methylation inhibitor,on the proliferation of androgen-sensitive prostate cancer line (LNCaP),and on its regulation of methylation on glutathione s transferaseP1 (GSTP1) and retinoic acid receptorβ2 (RARβ2) gene.Methods LNCaP cells were treated with 5-Aza-dc in different concentration,CCK8 method was used to detect the growth of LNCaP cells.The methylation of GSTP1 and RARβ2 gene in LNCaP cell was detected by nested methylation specific polymerase chain reaction (nMSP).Results The proliferation of LNCaP cells was inhibited after exposed to 5-Aza-dc.The methylation of GSTP1 and RARβ2 gene was changed from hypermethylation to demethylation by the 5-Aza-dc.These effects were dose-and time-dependent within certain concentration of 5-Aza-dc,but LNCaP cells grew better after 72 h than within 48 h when exposed to 5 Aza dc below 1.0 μmol/L.Also the methylation of GSTP1 and RARβ2 gene changed from hypermethylation to demethylation by the 5-Aza-dc was not different when exposed to 5-Aza-dc below 1.0 μmol/L within 72 h and 48 h.Conclusions 5-Aza-dc may effectively inhibit the growth of LNCaP cells and reverse the DNA methylation damage in some tumor suppressor genes,but the continuity and stability of low dose 5-Aza-dc is changeable.The study will provide a research basis for clinical treatment.