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

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.

Medienart:

Artikel

Erscheinungsjahr:

2005

Erschienen:

2005

Enthalten in:

Zur Gesamtaufnahme - volume:11

Enthalten in:

World journal of gastroenterology - 11(2005), 17 vom: 07. Mai, Seite 2552-6

Sprache:

Englisch

Beteiligte Personen:

Jacob, Dietmar [VerfasserIn]
Schumacher, Guido [VerfasserIn]
Bahra, Marcus [VerfasserIn]
Davis, John [VerfasserIn]
Zhu, Hong-Bo [VerfasserIn]
Zhang, Li-Dong [VerfasserIn]
Teraishi, Fuminori [VerfasserIn]
Neuhaus, Peter [VerfasserIn]
Fang, Bing-Liang [VerfasserIn]

Themen:

Apoptosis Regulatory Proteins
DNA-Binding Proteins
EC 2.7.7.49
Journal Article
Membrane Glycoproteins
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
TNF-Related Apoptosis-Inducing Ligand
TNFSF10 protein, human
Telomerase
Tumor Necrosis Factor-alpha

Anmerkungen:

Date Completed 22.06.2005

Date Revised 30.04.2019

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM154982725