CAJ | 학술논문

目的:探讨多西紫杉醇治疗男性雄激素抵抗前列腺癌(castration-resistant prostate cancer,CRPC)的分子机制.方法:前列腺癌细胞株LNCaP、PC-3和CW22-rv1体外培养后,通过蛋白质印迹、细胞转染、荧光素酶分析、细胞存活率分析等试验分析多西紫杉醇(Docetaxel,Doc)处理后细胞株的存活、AR及p-c-jun的表达情况及其与细胞生存的关系,同时实时定量PCR检测相应mRNA的表达情况.结果:多西紫杉醇对不同前列腺癌细胞株的敏感性不同,其中PC-3细胞最敏感,CW22-rv1和LNCaP细胞中度敏感,其敏感性与p-c-jun表达呈负相关.转染c-jun基因可降低细胞对多烯紫杉醇的敏感性,而PC-3细胞转染c-jun和AR基因后则可以使细胞恢复到中等程度敏感性,细胞存活率为30%.长期暴露于Bicalutmide(比卡鲁胺)后的LNCaP细胞经Doc处理后PSA蛋白表达增加,AR蛋白表达水平降低,AR的mRNA却增加.结论:p-c-jun降低前列腺癌细胞株对多西紫杉醇的敏感性,而AR可以增加前列腺癌细胞株对多西紫杉醇的反应,AR的上调降低c-jun/p-c-jun的转录活性,从而增加前列腺癌细胞株对Doc的反应,可能是Doc治疗前列腺癌的机制之一.
목적:탐토다서자삼순치료남성웅격소저항전렬선암(castration-resistant prostate cancer,CRPC)적분자궤제.방법:전렬선암세포주LNCaP、PC-3화CW22-rv1체외배양후,통과단백질인적、세포전염、형광소매분석、세포존활솔분석등시험분석다서자삼순(Docetaxel,Doc)처리후세포주적존활、AR급p-c-jun적표체정황급기여세포생존적관계,동시실시정량PCR검측상응mRNA적표체정황.결과:다서자삼순대불동전렬선암세포주적민감성불동,기중PC-3세포최민감,CW22-rv1화LNCaP세포중도민감,기민감성여p-c-jun표체정부상관.전염c-jun기인가강저세포대다희자삼순적민감성,이PC-3세포전염c-jun화AR기인후칙가이사세포회복도중등정도민감성,세포존활솔위30%.장기폭로우Bicalutmide(비잡로알)후적LNCaP세포경Doc처리후PSA단백표체증가,AR단백표체수평강저,AR적mRNA각증가.결론:p-c-jun강저전렬선암세포주대다서자삼순적민감성,이AR가이증가전렬선암세포주대다서자삼순적반응,AR적상조강저c-jun/p-c-jun적전록활성,종이증가전렬선암세포주대Doc적반응,가능시Doc치료전렬선암적궤제지일.
Objective:The present study investigated the biochemical mechanism of docetaxel (Doc) for the treatment of castra-tion-resistant prostate cancer (CRPC). Methods:The prostate cancer cell lines PC-3, LNCaP, and CW22-rv1 were grown in vitro. The expression of c-Jun and the androgen receptor (AR), the relationship between their expression levels, and the viability of LNCaP, PC-3, and CW22-rv1 cells after exposure to Doc were studied in vitro by immunoblot, luciferase, and viability assays. Furthermore, the ex-pression of AR mRNA was analyzed by quantitative real-time polymerase chain reaction (RT-PCR). Results:Doc therapy elicited dif-ferent responses in the different cell lines. PC-3 cells were the most sensitive to treatment, whereas a moderate response was observed in CW22-rv1 and LNCaP cells. The sensitivity and response to Doc was negatively correlated with the level of phosphorylated c-Jun (p-c-Jun) expression. Transfection of the c-jun gene into cell lines decreased their response to Doc treatment, whereas cotransfection of the c-jun and AR genes restored the sensitivity of PC-3 to a moderate degree, with 30%viability was 30%. After long-term exposure to bicalutamide (cas), the Doc-treated LNCaP cells demonstrated increased levels of the prostate specific antigen (PSA). Likewise the AR protein levels decreased with increasing AR mRNA expression. Conclusion: This study demonstrated that the level of p-c-Jun de-creased the response of PC cells to Doc treatment, but the level of AR increases PC cells response to Doc treatment. The increased AR level inhibits c-Jun/p-c-Jun transcriptional, which decreases the protective effects of Doc in PC cells.