Article
Suppression of pancreatic tumor growth in liver by systemic administration of the TRAIL Gene driven by the hTERT Promoter
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Published: | March 20, 2006 |
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Backround: Despite the availability of many therapeutic strategies and the advent of new therapeutic agents, the 5 year-survival of pancreatic cancer after diagnosis is below 5 %. Therefore, new therapeutic approaches for pancreatic cancer, especially for liver metastasis are required. In the current study we determined the combination effect of the TRAIL gene and gemcitabine in treatment of a pancreatic tumor model in the liver.
Methods: An adenoviral vector with RGD-modified fibers, expressing from the human telomerase reverse transcriptase (hTERT) promoter (designated Ad/TRAIL-F/RGD) was constructed and its antitumor activity in combination with gemcitabine was evaluated in two pancreatic cancer in vitro and in a pancreatic tumor model in nu/nu nude mice in the liver in vivo.
Results: Treatment with Ad/TRAIL-F/RGD elicited a high rate of apoptosis in human pancreatic cancer cell lines in vitro. The combination of TRAIL gene therapy and gemcitabine revealed a synergistic effect. The systemic administration of Ad/TRAIL-F/RGD via tail vein in combination with gemcitabine significantly suppressed tumor growth of pancreatic cancer in the liver, in comparison to the control group, without obvious toxic effects.
Conclusions: Our results suggest that TRAIL gene therapy in combination with gemcitabine could be a potent therapeutic approach for the treatment of advanced pancreatic cancer.