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LHRH 类似物对肝癌裸鼠移植瘤生长的影响

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World Chin J Digestol, 2002 July;10(7):759-764

世界华人消化杂志 ISSN 1009-3079 CN 14-1260/R

2002 年版权归世界胃肠病学杂志社

http://www.wendangku.net/doc/9a91a770f242336c1eb95eb8.html

•肝癌 LIVER CANCER•

LHRH类似物对肝癌裸鼠移植瘤生长的影响张金山,王 红,黄威权,孙 岚,黄高升,张远强

张金山,王红,黄威权,孙岚,张远强,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黄高升,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

张金山,男,1965-12-27生,黑龙江省克山县人,汉族,医学博士,讲师.国家自然科学基金资助课题,No39900142

项目负责人张金山,710033陕西省西安市长乐西路169号,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. jszhang@http://www.wendangku.net/doc/9a91a770f242336c1eb95eb8.html 电话:029-******* 传真:029-*******

收稿日期 2002-05-28 接受日期 2002-06-11

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

Jin-Shan Zhang, Hong Wang, Wei-Quan Huang,

Lan Sun, Gao-Sheng Huang, Yuan-Qiang Zhang

Jin-Shan Zhang, Hong Wang, Wei-Quan Huang, Lan Sun, Department of Histology and Embryology, Xi'an 710032, Shaanxi Province, China Gao-sheng Huang, Department of Pathology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China

Jin-shan Zhang, Department of Histology and Embryology, Xi'an 710032, Shaanxi Province, China

Supported by Nature Science Fund of China, No.39900142 Correspondence to: Jin-Shan Zhang, Department of Histology and Embryology, Fourth Military Medical University, 169 Changle West Road, Xi’ an 710032 China. jszhang@http://www.wendangku.net/doc/9a91a770f242336c1eb95eb8.html Received 2002-05-28 Accepted 2002-06-11

Abstract

AIM: T o 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 endocrinotherapy 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 2.4×106 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±738.3mm3 versus 4223.45±1027.6mm3 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 xenografts (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 on hepatocarcinoma cells growth.

Zhang JS, Wang H, Huang WQ, Sun L , Huang GS,Zhang YQ. Growth inhibition of luteinizing hormone-releasing hormone analog on hHCC hepatocarcinoma cell xenografts in nude mice. Shijie Huaren Xiaohua Zazhi 2002; 10(7): 759-764

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±738.3mm3)明显小于对照组裸鼠的肿瘤体积(4223.4±1027.6mm3),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% vs56.4%, 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