LHRH类似物对肝癌裸鼠移植瘤生长的影响  

Growth inhibition of luteinizing hormone-releasing hormone analog on hHCC hepatocarcinoma cell xenografts in nude mice

作　　者：张金山[1] 王红[1] 黄威权[1] 孙岚[1] 黄高升[2] 张远强[1] 

机构地区：[1]中国人民解放军第四军医大学基础部组织学与胚胎学教研室,陕西省西安市710033 [2]中国人民解放军第四军医大学基础部病理学教研室,陕西省西安市710033

出　　处：《世界华人消化杂志》2002年第7期759-764,共6页World Chinese Journal of Digestology

基　　金：国家自然科学基金;№39900142

摘　　要：目的:观察LHRH类似物的体内抗肝癌细胞增生活性,为LHRH类似物用于肝癌的内分泌治疗提供实验依据。方法:实验选用5-7周龄♂BALB/c裸鼠20只,分治疗组(丙氨瑞林瘤内注射组)和对照组(生理盐水瘤内注射组),用人肝癌hHCC细胞系建立肝癌荷瘤裸鼠模型,观察LHRH类似物丙氨瑞林(LHRH-A)对裸鼠移植瘤生长的影响;并分别用H-E染色和免疫细胞化学技术检测瘤组织的病理组织学改变和GnRH受体及凋亡蛋白Bax表达的变化。结果:LHRH-A瘤内注射(剂量为75μg/d)可显著抑制肝癌移植瘤的生长。治疗3 wk后治疗组裸鼠肿瘤体积(1885.9±738.3mm^3)明显小于对照组裸鼠的肿瘤体积(4223.4±1027.6mm^3),两组间有统计学差异(P<0.005);LHRH-A治疗3wk后的抑瘤率可达58％;治疗组裸鼠存活期(87.8±5.3d)较对照组(64.6±6.8d)显著延长(P<0.05);治疗3wk后病理组织学发现治疗组瘤组织中癌细胞核分裂象减少,腺样癌组织、凋亡细胞数增多;治疗组瘤组织中表达GnRH受体的癌细胞数增加(72.5％ vs 56.4％,P<0.05),Bax阳性细胞比率增加(53.8％ vs 41.5％,P<0.05)。结论:LHRH-A具有显著抑制肝癌裸鼠移植瘤细胞增生的活性,LHRH受体和凋亡蛋白Bax可能参与了LHRH-A对肝癌细胞增生的抑制作用。AIM: To observe the in vivo anti-proliferative effect of luteinizing hormone-releasing hormone analog (LHRH-A) on hepatocellular carcinoma (HCC) cell, and to provide the experimental evidence for LHRH-A in the endocrinobherapy of HCC. METHODS: In vivo action of LHRH-A on HCC cell growth was determined in a nude mouse model with hHCC cells subcutaneously transplanted, and each of twenty intact athymic nude mice (5 to 7 weeks old) was injected into 2.4×10~6 cells. On the day 14 after transplantation, the mice were divided equally into treatment group and control group. The treated animals received intralesionally LHRH-A 75mg per mouse per day, and control mice received the same amount of normal saline. Histological hematoxylin-osin staining and immunocytochemical SABC technique were employed to detect the histopathological changes and expression of LHRH receptor and Bax in HCC xenografts. RESULTS: LHRH-A at the dose of 75 mg per mouse per day used intralesionally can inhibit the tumor growth by shrinking the tumor volume and prolonging the survival time. After 3 week's treatment, the tumor inhibiting rate was 58％; the treatment group had a mean tumor volume of 1885.9±738.3mm^3 versus 4223.45±1:1027.6mm^3 for the control group (P<0.01); the mean survival time of mice in the treatment group(87.8±5.3d) was significantly longer than that of control group (64.6±6.8d, P<0.05). Histological examination showed that the number of carcinoma cells with nuclear mitotic figure was decreased and well-differentiated adenocarcinomas and apoptotic-like cells were increased in LHRH-A treated HCC xenografts. LHRH-A can up-regulate the LHRH receptor by increasing the LHRH-R positive cell number in the xenograffs (72.5％ vs 56.4％, P<0.05); and Bax positive cell percentage was also increased in LHRH-A treatment group compare with control (53.85％ vs 41.5％, P<0.05). CONCLUSIONS: LHRH-A is effective in inhibiting the hepatocarcinoma cell proliferation in vivo, LHRH-R and Bax may be involved in the inhibitory effect of LHRH-A

关 键 词：LHRH类似物 肝癌 裸鼠 移植瘤 

分 类 号：R735.7[医药卫生—肿瘤]