雄激素剥夺治疗对前列腺癌癌干细胞的影响

摘要

目的 探讨雄激素剥夺治疗(ADT)对前列腺癌癌干细胞(PrCSC)比例及干细胞相关基因的影响.方法 由雄激素依赖性前列腺癌细胞系LNCaP诱导出雄激素非依赖性前列腺癌细胞系LNCaPAI,流式细胞技术检测ADT对LNCaP中PrCSC比例以及雄激素对LNCaPAI中PrCSC比例的影响,Western blot及实时定量PCR检测BMI-1、ABCG2和NANOG的变化.结果 由LNCaP诱导出LNCaPAI细胞,LNCaP细胞中PrCSC的比例为0.04％.ADT 4周后PrCSC的比例增加至0.23％,6个月后形成LNCaPAI时则达到0.74％.ADT3周后,BMI-1、NANOG、ABCG2的表达逐渐增高,LNCaPAI中BMI-1、NANOG、ABCG2表达明显高于LNCaP.双氢睾酮作用于LNCaPAI后PrCSC的比例逐渐下降,第2周时下降至0.43％,第3周时下降至0.37％,第4周下降至0.33％.同时BMI-1、NANOG和ABCG2的表达逐渐降低.结论 ADT可以使LNCaP逐渐形成LNCaPAI,此时PrCSC比例增加,同时干细胞相关基因表达增加.双氢睾酮可以减少雄激素非依赖性前列腺癌中PrCSC比例.间断雄激素治疗可能是治疗前列腺癌的较好选择.%Objective To investigate the effect of androgen deprivation therapy (ADT) on ratio of prostate cancer stem cell (PrCSC) and the gene expression relative to stem cell. Methods An androgen-independent subline (LNCaPAI) was established by continuously cultur- ing the LNCaP cells in the medium without androgen. After the LNCaP cells were ablated of androgen, the proportion of PrCSC were assessed by flow cytometry analysis and the expressioas of BMI-1,ABCG2 and NANOG were assessed by Western blot and real-time RT-PCR. After cultured with androgen,the proportion of PrCSC and expression of BMI-UABCG2 and NANOG in LNCaPAI were assessed. Results The LNCaPAI subline were established from androgen-dependent LNCaP cells. In the LNCaP cell line,the CD44VCD24- subpopulation (PrCSC) was rare (0.04%), whereas the LNCaPAI cell line had a more prevalent CD447CD24- population (0.74%). After the LNCaP cells were cultured in an androgen deprivation condition,the CD44VCD24- subpopulation was increased. The expressions of BMI-l,ABCG2 and NANOG were increased after the LNCaP cells cultured in an androgen deprivation condition. The CD44+/CD24- subpopulation was significantly decreased when LNCaPAI cells were cultured with androgen. And the expressions of BMI-l,NANOG and ABCG2 were decreased,too. Conclusion It was found for the first time in our study that the CD44+/CD24- subpopulation was increased in androgen-dependent prostate cancer after androgen deprivation. We also found that the CD447CD24" subpopulation was decreased in LNCaPAI cells after androgen treatment. So the intermittent endocrinological treatments might be a good choice for the patients with prostate cancer.