他莫昔芬治疗乳腺癌异种移植瘤裸鼠子宫病理改变

Tamoxifen treated breast cancer xenograft in nude mice and uterine pathological changes

目的研究经他莫昔芬治疗后乳腺癌异种移植瘤裸鼠的子宫病理改变,及孕激素治疗是否会影响乳腺癌细胞的增生及他莫昔芬的治疗效果。方法将25只裸鼠皮下植入雌二醇(estradiol,E2)缓释片(0.72 mg/60 d),并建立MCF7乳腺癌细胞荷瘤模型,记录肿瘤体积,荷瘤43 d后,将裸鼠采用数字表法随机分为4个组,每组6只,分别为:安慰剂组、黄体酮组、他莫昔芬组、他莫昔芬联合黄体酮组。56 d后,处死裸鼠取瘤体及子宫,进行HE染色及肿瘤生长曲线绘制。结果裸鼠肿瘤生长速度结果显示:与安慰剂组相比,单用黄体酮未促进乳腺癌的额外增生(P>0.05),他莫昔芬治疗后,乳腺癌组织体积明显缩小(P<0.01)。裸鼠肿瘤HE染色可见:肿瘤组织较疏松,肿瘤细胞数量明显减少,可见坏死的肿瘤细胞及中性粒细胞和淋巴细胞浸润。子宫内膜HE染色结果显示,子宫腺体数目增多,腺细胞核大深染,部分出现异型性,出现子宫内膜不典型增生的病理改变。子宫腺体个数统计结果显示:与安慰剂组相比,经他莫昔芬治疗后的子宫内膜腺体数量增加明显(P<0.01),单用孕激素子宫内膜腺体数量无明显增加(P>0.05)。结论在乳腺癌异种移植瘤裸鼠中,他莫昔芬治疗后肿瘤体积明显缩小,但子宫腺体明显增加,呈不典型增生病理改变;单用孕激素未促进乳腺癌细胞明显增生,子宫内膜无明显增生,孕激素的应用不能拮抗他莫昔芬导致的子宫内膜不典型增生。

Objective To investigate the pathological changes of uterus in nude mice with breast cancer xenograft treated with tamoxifen(TAM),and effect of progesterone treatment on the proliferation of breast cancer and therapeutic efficacy of tamoxifen.Methods Prospective,randomized,placebo-controlled four-arm study in xenotransplantations: MCF7 cells were injected into nude mice.Estradiol(E2) pellets were implanted.After 43 days,the breast cancer xenograft was treated with progesterone(P) or TAM or TAM plus P or placebo.All four groups(6 mice/group) were further monitored for 56 days.After 56 days,the mice were sacrificed and take the tumor and uterus.Fresh tissue was immediately stored in 4% paraformaldehyde for hematoxylin and eosin(HE) staining and tumor growth curve mapping.Results Tumor growth curve showed that progesterone group did not promote additional proliferation of breast cancer compared with placebo group(P>0.05).Breast cancer tissue volume decreased significantly after tamoxifen treatment(P< 0.01).The HE staining result showed that the tumor tissue was loose connective and the number of tumor cells decreased.Endometrium HE staining showed that the number of glands increased,and glands cells were hyperchromatic,some of which presented atypia and pathological results of endometrial dysplasia.Compared with the placebo group,the number of endometrial glands increased significantly after tamoxifen treatment(P<0.01),while that of the progesterone group did not increase(P>0.05).Conclusion In the nude mice with breast cancer,the tumor volume was significantly reduced after tamoxifen treatment,but the glands were increased,indicating endometrial dysplasia.Progesterone alone did not promote the obvious proliferation of xenotransplantations,without obvious endometrial hyperplasia,Therefore the application of progesterone did not significantly antagonize tamoxifen.