溴隐亭与肿瘤坏死因子-α对裸鼠肝癌MDR1模型中逆转肝细胞癌多药耐药的协同作用。

Synergistic effect of bromocriptine and tumor necrosis factor-alpha on reversing hepatocellular carcinoma multidrug resistance in nude mouse MDR1 model of liver neoplasm.

作者信息

Ding Lei, Chen Xiao-Ping, Zhang Zhi-Wei, Guan Jian, Zhang Wan-Guang, Wang Hai-Ping, Wang Zhi-Hui, Li Chun-Lei

机构信息

Hepatic Surgery Center, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.

出版信息

World J Gastroenterol. 2005 Sep 28;11(36):5621-6. doi: 10.3748/wjg.v11.i36.5621.

DOI:10.3748/wjg.v11.i36.5621

PMID:16237754

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4481477/

Abstract

AIM

To investigate the effect of bromocriptine (BCT) and tumor necrosis factor-alpha (TNF-alpha) on hepatocellular carcinoma (HCC) multidrug resistance (MDR) in nude mouse MDR model of liver neoplasm.

METHODS

Human hepatocarcinoma cell line HepG(2), drug resistant hepatocarcinoma cell line HepG(2)/adriamycin (ADM) and hepatocarcinoma cell line transfected with TNF-alpha gene HepG(2)/ADM/TNF were injected into the liver of nude mice via orthotopic implantation and MDR model of liver neoplasm in vivo was established (HepG(2), ADM, TNF, BCT groups). Among these groups, BCT group and TNF group were treated with BCT through gastric canal. Each group was divided into control group and chemotherapy group. Size and weight of the tumor were measured. Furthermore, tumor histological character and growth of the nude mice were observed and their chemosensitivity was tested. MDR-associated genes and proteins (MRP, LRP) of implanted tumors were detected by immunohistochemistry, reverse transcriptase polymerase chain reaction, and apoptosis rate of hepatocarcinoma cells was detected by TUNEL assay.

RESULTS

The nude mouse model of each cell line was inoculated successfully. The tumor growth rate and weight were significantly different among groups. After chemotherapy, abdominal cavity tumor growth inhibition rate was higher in BCT group (67%) compared to ADM and TNF groups, and similar to HepG(2) group (54%). MDR1 and LRPmRNA could be detected in all groups, but TNF-alpha was detected only in TNF and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF and BCT groups was low similar to HepG(2) group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups with TUNEL assay.

CONCLUSION

BCT and TNF-alpha can reverse HCC MDR in nude mouse MDR1 model of liver neoplasm.

摘要

目的

在裸鼠肝癌多药耐药（MDR）模型中研究溴隐亭（BCT）和肿瘤坏死因子-α（TNF-α）对肝癌（HCC）多药耐药的影响。

方法

将人肝癌细胞系HepG(2)、耐药肝癌细胞系HepG(2)/阿霉素（ADM）以及转染TNF-α基因的肝癌细胞系HepG(2)/ADM/TNF通过原位植入法接种到裸鼠肝脏内，建立体内肝癌MDR模型（HepG(2)、ADM、TNF、BCT组）。其中，BCT组和TNF组经胃管给予BCT。每组再分为对照组和化疗组。测量肿瘤大小和重量。此外，观察裸鼠肿瘤组织学特征和生长情况，并检测其化疗敏感性。通过免疫组织化学、逆转录聚合酶链反应检测植入肿瘤的多药耐药相关基因和蛋白（MRP、LRP），采用TUNEL法检测肝癌细胞凋亡率。

结果

各细胞系裸鼠模型均成功接种。各组肿瘤生长速率和重量差异显著。化疗后，BCT组腹腔肿瘤生长抑制率（67%）高于ADM组和TNF组，与HepG(2)组（54%）相近。所有组均可检测到MDR1和LRPmRNA，但仅在TNF组和BCT组检测到TNF-α。此外，TNF组和BCT组肿瘤的MDR1和LRP蛋白表达与HepG(2)组相似较低。TUNEL法检测显示，BCT组肝癌细胞凋亡率远高于其他组。