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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

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World Journal of Gastroenterology 2005年第17期11卷 2552-2556页

作者： dietmarjacob GuidoSchumacher MarcusBahra JohnDavis Hong-BoZhu Li-DongZhang FuminoriTeraishi PeterNeuhaus Bing-LiangFang DepartmentofGeneral VisceralandTransplantationSurgeryHumboldtUniversityofBerlinCharitéVirchowClinicBerlinGermany DepartmentofThoracicandCardiovascularSurgery TheUniversityofTexasMDAndersonCancerCenter DepartmentofThoracicandCardiovascularSurgery TheUniversityofTexasMDAndersonCancerCenter//PrograminGeneTherapyandVirologyTheUniversityofTexasGraduateSchoolofBiomedicalSciencesHoustonTX77030USA

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 ***: 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. Phosphatebuffered 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/CMVGFP 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/TRAILF/RGD could become a potent therapeutic agent for the treatment of HCC, adenovirus resistant tumors, and CAR low or negative cancer cells.

关键词：肿瘤坏死因子细胞凋亡配合基因肝细胞肿瘤肿瘤细胞转录酶

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