Suppressing orthotopic pancreatic tumor growth with a fiber-modified adenovector expressing the TRAIL gene from the human telomerase reverse transcriptase promoter

Dietmar Jacob, John Davis, Hongbo Zhu, Lidong Zhang, Fuminori Teranishi, Shuhong Wu, Frank C. Marini, Bingliang Fang

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

An adenoviral vector with RGD-modified fibers and expressing the human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene from the human telomerase reverse transcriptase (hTERT) promoter (designated Ad/TRAIL-F/RGD) was constructed, and its antitumor activity was evaluated in vitro and in vivo. An in vitro study showed that treatment with Ad/TRAIL-F/RGD elicited a high rate of apoptosis in human pancreatic and colon cancer cell lines that were either susceptible or resistant to conventional adenovectors. In vivo study showed that direct administration of Ad/TRAIL-F/RGD to an orthotopic implantation tumor model established in the pancreatic tails of nu/ nu mice significantly suppressed tumor growth: tumors in the animals treated with Ad/TRAIL-F/RGD were approximately eight times smaller than those in animals treated with a control vector. We also evaluated hTERT promoter activity and the effect of Ad/TRAIL-F/RGD on mesenchymal stem cells. Our results showed that transgene expression from the hTERT promoter in human bone marrow mesenchymal stem cells was minimal. No adverse effect was observed in mesenchymal stem cells treated with Ad/TRAIL-F/RGD. Together, our results suggest that Ad/TRAIL-F/RGD could become a potent therapeutic agent for the management of pancreatic cancer.

Original languageEnglish
Pages (from-to)3535-3541
Number of pages7
JournalClinical Cancer Research
Volume10
Issue number10
DOIs
Publication statusPublished - May 15 2004
Externally publishedYes

Fingerprint

Mesenchymal Stromal Cells
Pancreatic Neoplasms
Growth
Apoptosis
Genes
Neoplasms
Transgenes
Colonic Neoplasms
Tail
Bone Marrow
Ligands
Cell Line
human TERT protein
In Vitro Techniques
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Suppressing orthotopic pancreatic tumor growth with a fiber-modified adenovector expressing the TRAIL gene from the human telomerase reverse transcriptase promoter. / Jacob, Dietmar; Davis, John; Zhu, Hongbo; Zhang, Lidong; Teranishi, Fuminori; Wu, Shuhong; Marini, Frank C.; Fang, Bingliang.

In: Clinical Cancer Research, Vol. 10, No. 10, 15.05.2004, p. 3535-3541.

Research output: Contribution to journalArticle

Jacob, Dietmar ; Davis, John ; Zhu, Hongbo ; Zhang, Lidong ; Teranishi, Fuminori ; Wu, Shuhong ; Marini, Frank C. ; Fang, Bingliang. / Suppressing orthotopic pancreatic tumor growth with a fiber-modified adenovector expressing the TRAIL gene from the human telomerase reverse transcriptase promoter. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 10. pp. 3535-3541.
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