Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2005; 11(10): 1496-1502
Published online Mar 14, 2005. doi: 10.3748/wjg.v11.i10.1496
Hepatocyte growth factor gene therapy prevents radiation-induced liver damage
Chau-Hua Chi, I-Li Liu, Wei-Yu Lo, Bor-Song Liaw, Yu-Shan Wang, Kwan-Hwa Chi
Chau-Hua Chi, I-Li Liu, Bor-Song Liaw, Yu-Shan Wang, Institute of Veterinary Science, National Taiwan University, Taiwan, China
I-Li Liu, Department of General Surgery, Veterans General Hospital-Taipei, National Yang-Ming University, Taipei, Taiwan, China
Wei-Yu Lo, Anawrahta Biotech. Co., Danshuei, Taipei 251, Taiwan, China
Yu-Shan Wang, Kwan-Hwa Chi, Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, China
Kwan-Hwa Chi, Cancer Center, Veterans General Hospital-Taipei, National Yang-Ming University, Taipei, Taiwan, China
Author contributions: All authors contributed equally to the work.
Supported by National Science Council grant NSC-91-275-9075-001 for the development of Boron Neutron Capture Therapy for Hepatoma Treatment
Correspondence to: Kwan-Hwa Chi, M.D., Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, 95, Wen-Chang Rd., Shih-Lin, Taipei, Taiwan, China. m006565@ms.skh.org.tw
Telephone: +886-2-28332211-2273 Fax: +886-2-28377582
Received: October 9, 2004
Revised: October 10, 2004
Accepted: November 19, 2004
Published online: March 14, 2005
Abstract

AIM: To transfer human HGF gene into the liver of rats by direct electroporation as a means to prevent radiation-induced liver damage.

METHODS: Rat whole liver irradiation model was accomplished by intra-operative approach. HGF plasmid was injected into liver and transferred by electroporation using a pulse generator. Control rats (n = 8) received electrogene therapy (EGT) vehicle plasmid and another 8 rats received HGF-EGT 100 μg 48 h before WLIR. Expression of HGF in liver was examined by RT-PCR and ELISA methods. Apoptosis was determined by TUNEL assay. Histopathology was evaluated 10 wk after whole liver irradiation.

RESULTS: Marked decrease of apoptotic cells and down-regulation of transforming growth factor-beta 1 (TGF-β1) mRNA were observed in the HGF-EGT group 2 d after liver irradiation compared to control animals. Less evidence of radiation-induced liver damage was observed morphologically in liver specimen 10 wk after liver irradiation and longer median survival time was observed from HGF-EGT group (14 wk) compared to control rats (5 wk). (P = 0.031).

CONCLUSION: For the first time it has been demonstrated that HGF-EGT would prevent liver from radiation-induced liver damage by preventing apoptosis and down-regulation of TGF-β1.

Keywords: Hepatocyte growth factor, HGF, Radiation, Liver, Electroporation, Electrogene therapy