Westin P, Brändström A, Damber J E, Bergh A
Department of Pathology, University of Umeå, Sweden.
Br J Cancer. 1995 Jul;72(1):140-5. doi: 10.1038/bjc.1995.290.
The positive effect of castration in prostatic cancer patients is considered to be related to the induction of apoptosis in androgen-dependent tumour cells. However, castration apparently does not induce apoptosis in the highly differentiated, androgen-sensitive Dunning R3327PAP rat prostatic adenocarcinoma. To elucidate potential mechanisms of apoptotic induction in this tumour model, rats with subcutaneously implanted tumours were treated with vehicle (I), castration+vehicle (C) or castration + 50 micrograms of oestradiol benzoate per day s.c. (C + E2). The effects on tumours were examined by morphometry, in situ end labelling (ISEL) of apoptotic cells and immunohistochemically with monoclonal antibodies to proliferating cell nuclear antigen (PCNA) at different time points up to 168 h after castration. Castration inhibited tumour growth and decreased the epithelial cell apoptotic rate (from 12 h) and epithelial cell proliferation rate (from 72 h) compared with that in the I group. Tumour volume, volume densities of epithelium and stroma and stroma cell proliferation rate remained constant in the C group during the study period. C + E2 treatment resulted in increases in cell proliferation in the stroma (from 12 h) and in the volume density of stroma (from 24 h) compared with that in the C and I groups. The number of apoptotic epithelial cells was increased (from 24 h), and this was followed by decreases in the volume density of epithelium (from 24 h), the epithelial cell proliferation rate (from 72 h) and the total tumour volume (from 72 h). We conclude that in the Dunning R3327PAP tumour model C + E2 treatment is more effective than castration alone. C+E2 treatment, in contrast to C, is able to induce tumour cell death and to decrease total tumour volume. The mechanism behind this effect is unknown, but it could be related to stimulatory effects of E2 in the tumour stroma.
去势对前列腺癌患者的积极作用被认为与雄激素依赖性肿瘤细胞凋亡的诱导有关。然而，去势显然不会诱导高度分化的、雄激素敏感的邓宁R3327PAP大鼠前列腺腺癌发生凋亡。为了阐明该肿瘤模型中凋亡诱导的潜在机制，将皮下植入肿瘤的大鼠分为三组进行处理：分别给予赋形剂（I组）、去势+赋形剂（C组）或去势+每天皮下注射50微克苯甲酸雌二醇（C + E2组）。在去势后长达168小时的不同时间点，通过形态计量学、凋亡细胞原位末端标记（ISEL）以及使用抗增殖细胞核抗原（PCNA）单克隆抗体进行免疫组织化学检测，来观察对肿瘤的影响。与I组相比，去势抑制了肿瘤生长，降低了上皮细胞凋亡率（从12小时开始）和上皮细胞增殖率（从72小时开始）。在研究期间，C组的肿瘤体积、上皮和基质的体积密度以及基质细胞增殖率保持恒定。与C组和I组相比，C + E2处理导致基质中的细胞增殖增加（从12小时开始）以及基质的体积密度增加（从24小时开始）。凋亡上皮细胞数量增加（从24小时开始），随后上皮的体积密度降低（从24小时开始）、上皮细胞增殖率降低（从72小时开始）以及肿瘤总体积降低（从72小时开始）。我们得出结论，在邓宁R3327PAP肿瘤模型中，C + E2处理比单纯去势更有效。与C组相比，C + E2处理能够诱导肿瘤细胞死亡并降低肿瘤总体积。这种作用背后的机制尚不清楚，但可能与E2对肿瘤基质的刺激作用有关。
