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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%。ADT 3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 effects of androgen deprivation therapy (ADT) on the proportion of prostate cancer stem cells (PrCSC) and the related genes of stem cells. Methods LNCaP androgen-independent prostate cancer cell line LNCaPAI was induced by androgen-dependent prostate cancer cell line LNCaP. The effect of ADT on PrCSC ratio in LNCaP and the ratio of androgen on LNCaPAI PrCSC were detected by flow cytometry. Western blot and real-time quantitative PCR detection of BMI-1, ABCG2 and NANOG changes. Results LNCaPAI cells were induced by LNCaP, and the proportion of PrCSC in LNCaP cells was 0.04%. PrCSC increased to 0.23% after 4 weeks of ADT and 0.74% after 6 months of formation of LNCaPAI. Three weeks after ADT, the expression of BMI-1, NANOG and ABCG2 gradually increased, and the expression of BMI-1, NANOG and ABCG2 in LNCaPAI was significantly higher than that in LNCaP. The proportion of PrCSC in DHNCaPAI decreased gradually after dihydrotestosterone administration, decreasing to 0.43% in the second week, 0.37% in the third week and 0.33% in the fourth week. At the same time, the expression of BMI-1, NANOG and ABCG2 gradually decreased. Conclusion ADT can make LNCaP gradually form LNCaPAI, when the proportion of PrCSC increases and the expression of stem cell related genes increases. Dihydrotestosterone reduces PrCSC ratio in androgen-independent prostate cancer. Intermittent androgen therapy may be a better choice for the treatment of prostate cancer.