Yamauchi Atsushi, Kawai Koji, Tsukamoto Sadamu, Ideyama Yukitaka, Shirai Tomoyuki, Akaza Hideyuki
Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba City, Ibaraki, Japan.
J Urol. 2006 Jan;175(1):348-52. doi: 10.1016/S0022-5347(05)00002-9.
We determined the chemopreventive effect of the antiandrogen bicalutamide (Zeneca Co., Ltd., Osaka, Japan) on Fisher 344 rat prostate carcinogenesis induced by DMAB (3,2'-dimethyl-4-aminobiphenyl) (Nard Co., Ltd., Osaka, Japan). We have previously reported that rat prostate microscopic carcinogenesis in this model was paradoxically enhanced when continuous treatment with bicalutamide was begun 20 weeks after the initiation of DMAB. In the current study we determined whether antiandrogen would promote or suppress the prostate carcinogenesis when administration was begun at a later period of carcinogenesis.
DMAB at a dose of 50 mg/kg was injected subcutaneously into all animals 10 times at 2-week intervals. To clarify the target lesions of bicalutamide we used 2 control groups (groups 1 and 2). Animals in groups 1 and 2 were autopsied at 60 and 74 weeks, respectively, after the initiation of DMAB. Treatment with bicalutamide began in the 60th week in group 3 rats and continued for 14 weeks. They were sacrificed in the 74th week.
Microscopic cancer was revealed in 27% of group 1 rats and the incidence was increased to 42% in group 2 (statistically not significant). Delayed bicalutamide treatment significantly suppressed the cancer lesion. No cancerous lesion was detected in the ventral or other lobes of the prostate of the rats in group 3. In contrast, bicalutamide did not affect the incidence of PIN. The difference in the incidence of PIN in groups 2 and 3 (84% and 78%, respectively) was not significant.
The current investigation indicates that, if bicalutamide is started in the later period, it can efficiently eradicate existing microscopic cancer. Despite this suppressive effect on microscopic cancer bicalutamide permits the persistence of PIN. The latter finding suggests that the sensitivity of PIN to antiandrogen might be more complicated than previously recognized.
我们确定了抗雄激素比卡鲁胺（阿斯利康制药有限公司，日本大阪）对由3,2'-二甲基-4-氨基联苯（DMAB）（日本大阪纳德有限公司）诱导的Fisher 344大鼠前列腺癌发生的化学预防作用。我们之前报道过，在DMAB启动20周后开始连续使用比卡鲁胺治疗时，该模型中大鼠前列腺微观癌发生反而增强。在当前研究中，我们确定了在致癌后期开始给药时，抗雄激素是会促进还是抑制前列腺癌发生。
以50mg/kg的剂量给所有动物皮下注射DMAB，每隔2周注射10次。为了明确比卡鲁胺的靶病变，我们使用了2个对照组（第1组和第2组）。第1组和第2组的动物分别在DMAB启动后60周和74周进行尸检。第3组大鼠在第60周开始用比卡鲁胺治疗，并持续14周。它们在第74周被处死。
第1组大鼠中有27%出现微观癌，第2组的发生率增加到42%（无统计学显著性）。比卡鲁胺延迟治疗显著抑制了癌病变。第3组大鼠前列腺腹侧或其他叶未检测到癌性病变。相比之下，比卡鲁胺不影响前列腺上皮内瘤变（PIN）的发生率。第2组和第3组PIN发生率的差异（分别为84%和78%）无统计学显著性。
当前研究表明，如果在后期开始使用比卡鲁胺，它可以有效根除现有的微观癌。尽管比卡鲁胺对微观癌有这种抑制作用，但它允许PIN持续存在。后一发现表明，PIN对抗雄激素的敏感性可能比之前认为的更复杂。
