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Abstract
ObjectiveThe objective of this study was to evaluate the anti-tumor effects of Ad/gTRAIL (an adenoviral vector in which expression of GFP and TRAIL is driven by a human telomerase reverse transcriptase promoter, hTERT) on malignant meningiomas and gliomas.BackgroundGliomas and meningiomas are the two most common types of human brain tumors. Currently there is no effective cure for recurrent malignant meningiomas or for gliomas. Ad/gTRAIL has been shown to be effective in killing selected lung, colon and breast cancer cells, but there have been no studies reporting its antitumor effects on malignant meningiomas. Therefore, we tested the antitumor effect of Ad/gTRAIL for the first time in human malignant meningioma and glioma cell lines, and in intracranial M6 and U87 xenografts.MethodsMaterials and Methods: Human malignant meningioma and glioma cells were infected with adenoviruses, Ad/gTRAIL and Ad/CMV-GFP. Cell viability was determined by proliferation assay. FACS analysis and quantification of TRAIL were used to measure apoptosis in these cells. We injected Ad/gTRAIL viruses in intracranial M6 and U87 xenografts, and measured the brain tumor volume, quantified apoptosis by TUNEL assay in the brain tumor tissue.ResultsOur studies demonstrate that in vitro/in vivo treatment with Ad/gTRAIL virus resulted in significant increase of TRAIL activity, and elicited a greater tumor cell apoptosis in malignant brain tumor cells as compared to treatment with the control, Ad/CMV-GFP virus without TRAIL activity.ConclusionsWe showed for the first time that adenovirus Ad/gTRAIL had significant antitumor effects against high grade malignant meningiomas as well as gliomas. Although more work needs to be done, our data suggests that Ad/gTRAIL has the potential to be useful as a tool against malignant brain tumors.
Highlights
Gliomas and meningiomas are the two most common types of human brain tumors
Our studies demonstrate that in vitro/in vivo treatment with Ad/gTRAIL virus resulted in significant increase of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activity, and elicited a greater tumor cell apoptosis in malignant brain tumor cells as compared to treatment with the control, Adenoviral vector with Cytomegalovirus promoter (Ad/CMV)-Green fluorescent protein (GFP) virus without TRAIL activity
We showed for the first time that adenovirus Ad/gTRAIL had significant antitumor effects against high grade malignant meningiomas as well as gliomas
Summary
Gliomas and meningiomas are the two most common types of human brain tumors. Currently there is no effective cure for recurrent malignant meningiomas or for gliomas. Ad/gTRAIL has been shown to be effective in killing selected lung, colon and breast cancer cells, but there have been no studies reporting its antitumor effects on malignant meningiomas. We tested the antitumor effect of Ad/gTRAIL for the first time in human malignant meningioma and glioma cell lines, and in intracranial M6 and U87 xenografts. Gliomas and meningiomas are the two most common types of human brain tumors. Meningiomas, on the other hand, are usually benign but often recur after surgical removal. It has been estimated that more than 85% of human cancers have high telomerase activity, which makes telomerase the most common tumor marker. The high tumor-specificity of hTERT gene expression and the fact that hTERT expression is mainly regulated at the transcriptional level have prompted the use of an hTERT promoter to drive suicide genes to induce specific cancer cell killing using liposome or adenovirus delivery systems [9]
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