Liver Cancer
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2005; 11(17): 2552-2556
Published online May 7, 2005. doi: 10.3748/wjg.v11.i17.2552
Fiber-modified adenoviral vector expressing the tumor necrosis factor-related apoptosis-inducing ligand gene from the human telomerase reverse transcriptase promoter induces apoptosis in human hepatocellular carcinoma cells
Dietmar Jacob, Guido Schumacher, Marcus Bahra, John Davis, Hong-Bo Zhu, Li-Dong Zhang, Fuminori Teraishi, Peter Neuhaus, Bing-Liang Fang
Dietmar Jacob, Guido Schumacher, Marcus Bahra, Peter Neuhaus, Department of General, Visceral and Transplantation Surgery, Humboldt University of Berlin, Charité Virchow Clinic, Berlin, Germany
John Davis, Hong-Bo Zhu, Li-Dong Zhang, Fuminori Teraishi, Bing-Liang Fang, Department of Thoracic and Cardiovascular Surgery, The University of Texas, MD Anderson Cancer Center
John Davis, Bing-Liang Fang, Program in Gene Therapy and Virology, The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Dietmar Jacob, Department of General, Visceral and Transplantation Surgery, Humboldt University of Berlin, Charité Virchow Clinic, Augustenburger Platz 1, 13353 Berlin, Germany. dietmar.jacob@charite.de
Telephone: +49-30-450552001 Fax: +49-30-450552900
Received: April 22, 2004
Revised: April 23, 2004
Accepted: July 27, 2004
Published online: May 7, 2005
Abstract

AIM: Because of a major resistance to chemotherapy, prognosis of hepatocellular carcinoma (HCC) is still poor. New treatments are required and gene therapy may be an option. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in multiple malignant tumors, and using adenoviral vectors has shown a targeted tumor-specific therapy. However, repeated administration of adenoviral vectors can lead to cell resistance, which may be caused by the initial coxsackie-adenovirus receptor (CAR). One technique to overcome resistance is the use of modified adenoviral vectors containing an Arg-Gly-Asp (RGD) sequence. In this study we constructed an adenoviral vector (designated Ad/TRAIL-F/RGD) with RGD-modified fibers, expressing the TRAIL gene from the human telomerase reverse transcriptase (hTERT) promoter, and evaluated its antitumor activity in HCC cell lines.

METHODS: To investigate the effects of Ad/TRAIL-F/RGD in human HCC cell lines Hep G2 and Hep 3b, cells were infected with Ad/CMV-GFP (vector control), Ad/gTRAIL (positive control), and Ad/TRAIL-F/RGD. Phosphate-buffered saline (PBS) was used as control. Cell viability was determined by proliferation assay (XTT), and apoptosis induction by fluorescence activated cell sorting (FACS).

RESULTS: Cells treated with Ad/TRAIL-F/RGD and Ad/gTRAIL showed a significantly reduced cell viability in comparison to PBS and Ad/CMV-GFP treatment in both cell lines. Whereas, treatment with PBS and Ad/CMV-GFP had no cell-killing effect. The reduced cell viability was caused by induction of apoptosis as shown by FACS analysis. The amount of apoptotic cells was similar after incubation with Ad/gTRAIL and Ad/TRAIL-F/RGD.

CONCLUSION: The new RGD modified vector Ad/TRAIL-F/RGD could become a potent therapeutic agent for the treatment of HCC, adenovirus resistant tumors, and CAR low or negative cancer cells.

Keywords: HCC, TRAIL, hTERT