Synergistic effect of bromocriptine and tumor necrosis factor-α on reversing hepatocellular carcinoma multidrug resistance in nude mouse MDR1 model of liver neoplasm
Synergistic effect of bromocriptine and tumor necrosis factor-α on reversing hepatocellular carcinoma multidrug resistance in nude mouse MDR1 model of liver neoplasm
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DOI：
10.3748/wjg.v11.i36.5621
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发表时间：
2005-09-28
影响因子：
4.3
通讯作者：
Li, Chun-Lei
中科院分区：
文献类型：
--
作者：
Ding, Lei;Chen, Xiao-Ping;Li, Chun-Lei
目的：探讨溴隐亭（BCT）和肿瘤坏死因子-α（TNF-α）对肝癌细胞增殖的影响肿瘤坏死因子-α（TNF-α）对肝癌多药耐药（MDR）的影响。人肝癌细胞系HepG（2），耐药肝癌细胞系HepG（2）/ADM和转染TNF-α基因的肝癌细胞系HepG（2）/ADM/ADM，将肿瘤坏死因子（TNF）原位移植于裸鼠肝内，建立肝癌体内多药耐药模型（HepG（2）组、ADM组、TNF组、BCT组）。其中BCT组和TNF组经胃管注入BCT。每组又分为对照组和化疗组。测量肿瘤的大小和重量。观察裸鼠移植瘤的组织学特征和生长情况，并检测其化疗敏感性。采用免疫组化、逆转录聚合酶链反应（RT-PCR）检测移植瘤的MDR相关基因和蛋白（MRP、LRP），TUNEL法检测移植瘤细胞的凋亡率。各组间肿瘤生长速度和重量差异有统计学意义。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。MDR 1和LRP mRNA在所有组中均能检测到，而TNF-α仅在TNF和BCT组中检测到。TNF组和BCT组肿瘤组织中MDR 1和LRP蛋白的表达与HepG（2）组相似。结论：BCT和TNF-α能逆转裸鼠肝癌MDR 1模型中肝癌细胞的多药耐药。(C)2005年WJG出版社和Elsevier Inc. All rights reserved.
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. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.