现代泌尿外科杂志
現代泌尿外科雜誌
현대비뇨외과잡지
Journal of Modern Urology
2015年
8期
584-587
,共4页
熊永江%刘纯青%戴志红%董相权%刘志宇
熊永江%劉純青%戴誌紅%董相權%劉誌宇
웅영강%류순청%대지홍%동상권%류지우
前列腺癌%PC3细胞%三氧化二砷%Hedgehog信号通路
前列腺癌%PC3細胞%三氧化二砷%Hedgehog信號通路
전렬선암%PC3세포%삼양화이신%Hedgehog신호통로
prostatic cancer%PC3 cells%arsenic trioxide%hedgehog signaling pathway
目的 探讨三氧化二砷(ATO)联合环杷明(cyclopamine,CYA)对非雄激素依赖前列腺癌PC3细胞增殖的影响及其分子学机制.方法 采用MTT比色法检测不同浓度ATO及CYA单独或联合治疗对不同时间点PC3细胞生长的抑制作用.应用裸鼠致瘤实验进一步验证ATO联合CYA对PC3细胞生长的影响.Western blot检测ATO联合CYA对PC3细胞内 Hedgehog (Hh)信号通路中重要蛋白Smoothened(Smo)、Patched (Ptch)及GLI1的影响.结果 ATO或CYA抑制PC3细胞生长呈现明显的剂量及时间依赖性,且两药联合对PC3细胞生长有协同杀伤作用.动物实验进一步证实ATO联合CYA较单剂量组更能明显抑制PC3细胞移植瘤的生长(P<0.05).Western blot 结果证实ATO和CYA联合较单剂量组更明显下调Smo、Ptch及GLI1的表达.结论 ATO联合CYA能协同抑制PC3细胞的生长,其机制可能是两药联合协同下调PC3细胞中 Hh信号通路的表达.
目的 探討三氧化二砷(ATO)聯閤環杷明(cyclopamine,CYA)對非雄激素依賴前列腺癌PC3細胞增殖的影響及其分子學機製.方法 採用MTT比色法檢測不同濃度ATO及CYA單獨或聯閤治療對不同時間點PC3細胞生長的抑製作用.應用裸鼠緻瘤實驗進一步驗證ATO聯閤CYA對PC3細胞生長的影響.Western blot檢測ATO聯閤CYA對PC3細胞內 Hedgehog (Hh)信號通路中重要蛋白Smoothened(Smo)、Patched (Ptch)及GLI1的影響.結果 ATO或CYA抑製PC3細胞生長呈現明顯的劑量及時間依賴性,且兩藥聯閤對PC3細胞生長有協同殺傷作用.動物實驗進一步證實ATO聯閤CYA較單劑量組更能明顯抑製PC3細胞移植瘤的生長(P<0.05).Western blot 結果證實ATO和CYA聯閤較單劑量組更明顯下調Smo、Ptch及GLI1的錶達.結論 ATO聯閤CYA能協同抑製PC3細胞的生長,其機製可能是兩藥聯閤協同下調PC3細胞中 Hh信號通路的錶達.
목적 탐토삼양화이신(ATO)연합배파명(cyclopamine,CYA)대비웅격소의뢰전렬선암PC3세포증식적영향급기분자학궤제.방법 채용MTT비색법검측불동농도ATO급CYA단독혹연합치료대불동시간점PC3세포생장적억제작용.응용라서치류실험진일보험증ATO연합CYA대PC3세포생장적영향.Western blot검측ATO연합CYA대PC3세포내 Hedgehog (Hh)신호통로중중요단백Smoothened(Smo)、Patched (Ptch)급GLI1적영향.결과 ATO혹CYA억제PC3세포생장정현명현적제량급시간의뢰성,차량약연합대PC3세포생장유협동살상작용.동물실험진일보증실ATO연합CYA교단제량조경능명현억제PC3세포이식류적생장(P<0.05).Western blot 결과증실ATO화CYA연합교단제량조경명현하조Smo、Ptch급GLI1적표체.결론 ATO연합CYA능협동억제PC3세포적생장,기궤제가능시량약연합협동하조PC3세포중 Hh신호통로적표체.
Objective To investigate the effect of arsenic trioxide (ATO) alone and in combination with cyclopamine (CYA) on the proliferation of PC3 cells and to further explore its molecular mechanism.Methods PC3 cells were treated with different concentrations of ATO and CYA alone or in combination for different periods,and cell viability was analyzed with MTT assay.PC-3 xenograft model was used to further investigate the antiproliferative effects of ATO combined with CYA.The expressions of Hh target genes Ptch,Smo,and Gli1 were determined by Western blot.Results The results of MTT displayed that ATO or CYA alone reduced the viability of PC3 cells in a concentration-dependent and time-dependent manner and exhibited a synergism.Combined treatment of the cells with ATO and CYA dramatically increased antiprolifera-tive effects in nude mice compared with ATO or CYA treatments alone (P<0.05).The combined treatment of ATO and CYA was much more effective than CYA or ATO alone in terms of down-regulating the Ptch,Smo,and Gli1 expressions in PC3 cells.Conclusions ATO showed synergism with CYA in inhibiting the growth of PC3 cells.The exact mechanism may in-volve downregulation of Hh pathway.
