Novel REIC/Dkk-3-encoding adenoviral vector as a promising therapeutic agent for pancreatic cancer

Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3), a tumor suppressor gene, is downregulated in various cancers. We previously reported the tumor-inhibitory effects of the REIC/Dkk-3 gene, delivered by a conventional adenoviral vector (Ad-CAG-REIC) in pancreatic cancer. Here, we dev...

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Veröffentlicht in:Cancer gene therapy 2016-08, Vol.23 (8), p.278-283
Hauptverfasser: Sawahara, H, Shiraha, H, Uchida, D, Kato, H, Nagahara, T, Iwamuro, M, Kataoka, J, Horiguchi, S, Watanabe, M, Sakaguchi, M, Takaki, A, Nouso, K, Nasu, Y, Kumon, H, Okada, H
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container_end_page 283
container_issue 8
container_start_page 278
container_title Cancer gene therapy
container_volume 23
creator Sawahara, H
Shiraha, H
Uchida, D
Kato, H
Nagahara, T
Iwamuro, M
Kataoka, J
Horiguchi, S
Watanabe, M
Sakaguchi, M
Takaki, A
Nouso, K
Nasu, Y
Kumon, H
Okada, H
description Reduced expression in immortalized cells (REIC)/dickkopf-3 (Dkk-3), a tumor suppressor gene, is downregulated in various cancers. We previously reported the tumor-inhibitory effects of the REIC/Dkk-3 gene, delivered by a conventional adenoviral vector (Ad-CAG-REIC) in pancreatic cancer. Here, we developed an Ad-REIC vector with a novel gene expression system, termed the super gene expression (SGE) system, and assessed its therapeutic effects relative to those of Ad-CAG-REIC in pancreatic cancer cells. Human pancreatic cancer cell lines ASPC1 and MIAPaCa2 were used. REIC/Dkk-3 expression was assessed by western blot analysis. Relative cell viability and apoptotic effects were examined in vitro . The anti-tumor effects of Ad-REIC treatment were assessed in the mouse xenograft model. Compared with Ad-CAG-REIC, Ad-SGE-REIC elicited a significant increase in REIC protein expression in the cells studied. Relative to Ad-CAG-REIC, Ad-SGE-REIC reduced cell viability and induced apoptosis in the ASPC1 and MIAPaCa2 cell lines in vitro , and achieved superior tumor growth inhibition in the mouse xenograft model. Compared with conventional Ad-REIC agents, Ad-SGE-REIC provided enhanced inhibitory effects against tumor growth. Our results indicate that Ad-SGE-REIC is an innovative therapeutic tool for pancreatic cancer.
doi_str_mv 10.1038/cgt.2016.31
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Adenoviridae - genetics
Analysis
Animals
Apoptosis
Apoptosis - genetics
Biomedical and Life Sciences
Biomedicine
Cancer cells
Care and treatment
Cell Line, Tumor
Cell Survival - genetics
Cell viability
Chemotherapy
Diagnosis
Disease Models, Animal
Gene Expression
Gene Order
Gene Therapy
Genetic Therapy
Genetic Vectors - administration & dosage
Genetic Vectors - genetics
Health aspects
Humans
Intercellular Signaling Peptides and Proteins - genetics
Intercellular Signaling Peptides and Proteins - metabolism
JNK Mitogen-Activated Protein Kinases - metabolism
Kinases
Medical innovations
Mice
original-article
Pancreatic cancer
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Pancreatic Neoplasms - therapy
Signal Transduction
Trinucleotide repeats
Tumor Burden - genetics
Tumor cell lines
Tumor suppressor genes
Tumors
Xenograft Model Antitumor Assays
Xenografts
title Novel REIC/Dkk-3-encoding adenoviral vector as a promising therapeutic agent for pancreatic cancer
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