α-双炔失碳酯对前列腺癌LNCaP裸鼠移植瘤生长影响的研究  

Effect of α-anordrin on the growth of transplanted tumor of prostate cancer cell LNCaP in nude mice

作　　者：万隽[1] 翁绳美[1] 林菁[1] 

机构地区：[1]福建医科大学药学院药理学系,福州350004

出　　处：《海峡药学》2008年第3期36-40,F0003,共6页Strait Pharmaceutical Journal

基　　金：福建省青年科技人才创新基金资助项目(No2002J045)

摘　　要：目的研究α-双炔失碳酯(α-anordrin)对前列腺癌雄激素依赖细胞系LNCaP裸鼠皮下移植瘤生长的影响并探讨其作用机制。方法建立前列腺癌雄激素依赖细胞系LNCaP裸鼠皮下移植瘤模型,将27只荷瘤裸鼠按肿瘤体积大小平均分为3组:对照组、α-双炔失碳酯1mg.kg-1组、5mg.kg-1组。皮下注射给药,隔天一次,给药周期30天,每隔5天测量肿瘤体积。于末次给药24h后摘眼球取血,测量血浆睾酮(T)、前列腺特异膜抗原(PSA)水平;取睾丸、精囊腺和前列腺称重;取肿瘤称重,并对瘤组织进行组织病理学检查和免疫组化Ki67、PCNA检测。计算肿瘤体积,抑瘤率,绘制生长曲线。结果α-双炔失碳酯给药组肿瘤体积、重量均小于给药组,1mg.kg-1组抑瘤率为34%(P<0.05),5mg.kg-1组抑瘤率为25%(P>0.05);给药组和对照组间血浆PSA含量无明显差别,PCNA和Ki67阳性表达率亦无差别。给药组裸鼠血浆T水平、睾丸、精囊腺重量显著低于对照组(P<0.01),前列腺重量亦有减轻。结论α-双炔失碳酯在低剂量下即可对前列腺癌雄激素依赖细胞系LNCaP裸鼠皮下移植瘤的生长产生抑制作用,并能显著降低裸鼠血浆T水平,抑制其性腺的正常生长。其抗肿瘤的机制可能与抑制体内雄激素分泌有关。OBJECTIVE To explore the effects of a-anordrin on the growth of androgen-dependent prostate cancer cell LNCaP transplanted in nude mice. METHODS The model of xenograft tumor in nude mice were es- tablished by inoculating androgen-dependent prostate cancer cell LNCaP into the back of nude mice subcutaneously, and twenty-seven xenografts were established successively. They were then divided into 3 groups by tumor volume： control, α-ANO ling·kg^- l, α-ANO 5mg·kg^- 1. α-ANO were administered every two days by subcutaneous, and tumor volume were measured every 5 days. All the mice were sacrificed after 30 days treatment, and the tumor, testis, seminal vesicle and prostate weights were measured and the T and PSA in serum were studied by the ELISA kit. The tumor weights inhibition rate were calculated. Immunohistochemistry of Ki67 and PCNA was done to study the effects of α-ANO on the proliferation of prostate cancer cell. H＆E stain was done to examine the difference in histopathology between control team and administration team. RESULTS In vivo α-ANO adminis- tration can reduce the weight and volume of LNCaP xenograft tumor.α-ANO can also decrease the T level in serum of nude mice and restrain the growth of testis, seminal vesicle and prostate, but do not influence the PSA level in serum. The α-ANO treated groups and the control group did not have statistical difference on the percent- age of Ki67 and PCNA positive cells.CONCLUSION α-anordrin can inhibit the growth of LNCaP xenograft tumor in the nude mice with low dose by its strong inhibiting effects on the secretion of T in serum.

关 键 词：Α-双炔失碳酯 前列腺癌 LNCAP 裸鼠 移植瘤 

分 类 号：R97[医药卫生—药品]