Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2016; 22(21): 5033-5041
Published online Jun 7, 2016. doi: 10.3748/wjg.v22.i21.5033
125I-labeled anti-bFGF monoclonal antibody inhibits growth of hepatocellular carcinoma
Peng-Hui Hu, Lan-Hong Pan, Patrick Ting-Yat Wong, Wen-Hui Chen, Yan-Qing Yang, Hong Wang, Jun-Jian Xiang, Meng Xu
Peng-Hui Hu, Lan-Hong Pan, Wen-Hui Chen, Meng Xu, Department of Oncology, the First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China
Patrick Ting-Yat Wong, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China
Yan-Qing Yang, Hong Wang, Jun-Jian Xiang, Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Jinan University, Guangzhou 510632, Guangdong Province, China
Author contributions: Hu PH and Pan LH contributed equally to this work; Xu M designed and supervised the research; Hu PH and Pan LH conducted experiments; Wong PTY, Chen WH, and Yang YQ analyzed the data; Wang H and Xiang JJ discussed the results; Hu PH and Pan LH co-wrote the manuscript and prepared all figures; all the authors have read and approved the paper to be published.
Supported by the National Natural Science Foundation of China, No. 81273814; and Guangdong Province Key Scientific Research Grant, No. 2013A022100031.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the First Affiliated Hospital of Jinan University, Guangzhou, China.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Laboratory Animal Center of Jinan University (IACUC protocol number: 20150305001).
Conflict-of-interest statement: The authors declare no potential conflicts of interest related to this paper.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Meng Xu, MD, PhD, Department of Oncology, the First Affiliated Hospital, Jinan University, No. 613 Huangpu Avenue West, Guangzhou 510632, Guangdong Province, China. xumengjinan@yahoo.com
Telephone: +86-20-38688908 Fax: +86-20-38688000
Received: February 2, 2016
Peer-review started: February 3, 2016
First decision: March 7, 2016
Revised: March 14, 2016
Accepted: March 30, 2016
Article in press: March 30, 2016
Published online: June 7, 2016
Processing time: 118 Days and 3.4 Hours
Abstract

AIM: To investigate the inhibitory efficacy of 125I-labeled anti-basic fibroblast growth factor (bFGF) monoclonal antibody (mAb) in hepatocellular carcinoma (HCC).

METHODS: bFGF mAb was prepared by using the 1G9B9 hybridoma cell line with hybridization technology and extracted from ascites fluid through a Protein G Sepharose affinity column. After labeling with 125I through the chloramine-T method, bFGF mAb was further purified by a Sephadex G-25 column. Gamma radiation counter GC-1200 detected radioactivity of 125I-bFGF mAb. The murine H22 HCC xenograft model was established and randomized to interventions with control (phosphate-buffered saline), 125I-bFGF mAb, 125I plus bFGF mAb, bFGF mAb, or 125I. The ratios of tumor inhibition were then calculated. Expression of bFGF, fibroblast growth factor receptor (FGFR), platelet-derived growth factor, and vascular endothelial growth factor (VEGF) mRNA was determined by quantitative reverse transcriptase real-time polymerase chain reaction.

RESULTS: The purified bFGF mAb solution was 8.145 mg/mL with a titer of 1:2560000 and was stored at -20 °C. After coupling, 125I-bFGF mAb was used at a 1: 1280000 dilution, stored at 4 °C, and its specific radioactivity was 37 MBq/mg. The corresponding tumor weight in the control, 125I, bFGF mAb, 125I plus bFGF mAb, and 125I-bFGF mAb groups was 1.88 ± 0.25, 1.625 ± 0.21, 1.5 ± 0.18, 1.41 ± 0.16, and 0.98 ± 0.11 g, respectively. The tumor inhibition ratio in the 125I, bFGF mAb, 125I plus bFGF mAb, and 125I-bFGF mAb groups was 13.6%, 20.2%, 25.1%, and 47.9%, respectively. Growth of HCC xenografts was inhibited significantly more in the 125I-bFGF mAb group than in the other groups (P < 0.05). Expression of bFGF and FGFR mRNA in the 125I-bFGF mAb group was significantly decreased in comparison with other groups (P < 0.05). Groups under interventions revealed increased expression of VEGF mRNA (except for 125I group) compared with the control group.

CONCLUSION: 125I-bFGF mAb inhibits growth of HCC xenografts. The coupling effect of 125I-bFGF mAb is more effective than the concomitant use of 125I and bFGF mAb.

Keywords: Basic fibroblast growth factor; 125Iodine; Monoclonal antibody; Hepatocellular carcinoma; Fibroblast growth factor receptor; Vascular endothelial growth factor

Core tip: The aim of this study was to investigate the inhibitory efficacy of 125I-basic fibroblast growth factor (bFGF) monoclonal antibody (mAb) in mice with hepatocellular carcinoma (HCC). 125I-bFGF mAb inhibited the growth of HCC xenografts (P < 0.05). The combination of 125I and bFGF mAb was more effective than the concomitant use of 125I and bFGF mAb. 125I-bFGF mAb also significantly reduced the expression of bFGF and fibroblast growth factor receptor (FGFR) mRNA (P < 0.05). Moreover, 125I-bFGF mAb downregulated platelet-derived growth factor mRNA and upregulated vascular endothelial growth factor mRNA.