Liver Cancer
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2005; 11(36): 5621-5626
Published online Sep 28, 2005. doi: 10.3748/wjg.v11.i36.5621
Synergistic effect of bromocriptine and tumor necrosis factor-α on reversing hepatocellular carcinoma multidrug resistance in nude mouse MDR1 model of liver neoplasm
Lei Ding, Xiao-Ping Chen, Zhi-Wei Zhang, Jian Guan, Wan-Guang Zhang, Hai-Ping Wang, Zhi-Hui Wang, Chun-Lei Li
Lei Ding, Xiao-Ping Chen, Zhi-Wei Zhang, Jian Guan, Wan-Guang Zhang, Hai-Ping Wang, Hepatic Surgery Center, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Zhi-Hui Wang, Chun-Lei Li, Department of Ultrasonography, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Author contributions: All authors contributed equally to the work.
Supported by the Clinical Key Program Point Subject Foundation of Ministry of Public Health, No. 2001-2003
Correspondence to: Professor Xiao- Ping Chen, Department of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China. chenxp@medmail.com
Telephone: +86-27-83662599 Fax: +86-27-83662851
Received: November 16, 2004
Revised: January 23, 2005
Accepted: January 26, 2005
Published online: September 28, 2005
Abstract

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

METHODS: Human hepatocarcinoma cell line HepG2, drug resistant hepatocarcinoma cell line HepG2/adriamycin (ADM) and hepatocarcinoma cell line transfected with TNF-α gene HepG2/ADM/TNF were injected into the liver of nude mice via orthotopic implantation and MDR model of liver neoplasm in vivo was established (HepG2, 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 HepG2 group (54%). MDR1 and LRPmRNA could be detected in all groups, but TNF-αwas detected only in TNF and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF and BCT groups was low similar to HepG2 group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups with TUNEL assay.

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

Keywords: Bromocriptine; Tumor necrosis factor-α; Hepatocellular carcinoma