前列腺癌内分泌治疗中阻断肾上腺源性雄激素时机的实验研究

Experimental study of the appropriate time to block adrenal androgens in endocrine therapy of prostate cancer

目的 探究在前列腺癌的内分泌治疗中阻断肾上腺源性雄激素的恰当时机.方法 2013年2月至2014年3月,采用LNCaP细胞建立雄激素依赖的前列腺癌SCID鼠模型.首先设置未去势和去势两组,每组6只,于第1、4、7、10、14、17、21、28、35、42、49、56天检测血清PSA并测量肿瘤体积,以确定去势后前列腺癌复发时间点;然后设置去势同时去除肾上腺组、去势后复发时间点去除肾上腺组以及去势后复发时间点假肾上腺切除术组3组,每组6只,按上述时间点检测血清PSA、测量肿瘤体积,并在第56天收获5组的肿瘤组织以检测组织内睾酮浓度.统计分析比较各组肿瘤进展情况的差异.结果 去势组的复发时间为第14天,去势同时去除肾上腺组为第21天,去势后复发时间点去除肾上腺组为第35天.去势同时去除肾上腺组和去势后复发时间点去除肾上腺组肿瘤组织内睾酮浓度分别为（2.69±0.21）和（2.16±0.13） pmol/g,组间比较差异有统计学意义（P＜0.05）.结论 相对于去势同时去除肾上腺疗法,去势后复发时间点去除肾上腺疗法的肿瘤进展较慢.

Objective To explore the appropriate time to block adrenal androgens in endocrine therapy of prostate cancer.Methods An human androgen-dependent prostate carcinoma xenograft model in SCID mice was established with LNCaP cells.Firstly,the serum PSA and tumor volume of 2 groups （castrated and not castrated） were measured on the 1,4,7,10,14,17,21,28,35,42,49 and 56 day to determine the recurrent time of prostate cancer after castration.Secondly,3 different groups of castration and adrenalectomy at the same time,adrenalectomy in recurrence after castration and sham adrenalectomy in recurrent after castration,were set to measure the serum PSA and tumor volume on the 1,4,7,10,14,17,21,28,35,42,49 and 56 day.The tumor tissues of 5 groups were harvested to measure testosterone concentration,and tumor progress in these groups was compared.Results The recurrence time was 14 days in castrated group,21 days in group with castration and adrenalectomy at the same time and 35 days in group with adrenalectomy in recurrence after castration.The testosterone concentration in tumor tissues was （2.69± 0.21） pmol/g in the group with castration and adrenalectomy at the same time,and （2.16±0.13） pmol/g in the group with adrenalectomy in recurrence after castration,and the difference was significant （P＜0.05）.Conclusion Compared with the therapy of castration and adrenalectomy at the same time,the therapy of adrenalectomy in recurrence after castration may have slower progress course in prostate cancer.