Potential of adenovirus‐mediated REIC/Dkk‐3 gene therapy for use in the treatment of pancreatic cancer

Abstract

Ad-REIC induces apoptosis and inhibits tumor growth in pancreatic cancer cell lines. REIC/Dkk-3 gene therapy is an attractive therapeutic tool for pancreatic cancer.

Improving lipoprotein profiles by liver-directed gene transfer of low density lipoprotein receptor gene in hypercholesterolaemia mice

“…Several viral vectors including adenovirus, lentivirus and adeno-associated virus (AAV), which are able to efficiently introduce foreign DNA into a wide range of cells, have been routinely used in gene therapy. Owing to large capacity for foreign DNA and easy to prepare high titer, the replication-defective adenovirus has become a common tool for delivery of therapeutic genes (Lugenbiel et al 2012;Westphal et al 2013;Uchida et al 2014;Zeng et al 2014). However, as a nonintegrative delivery system, adenoviral vectors can only allow transient episomal expression of foreign genes in the host cells which results in lost of transgenes expression overtime by dilution in dividing cells or degeneration in nondividing cells.…”

A Novel Role of Dickkopf-Related Protein 3 in Macropinocytosis in Human Bladder Cancer T24 Cells

“…Autophagy is a process of self-digestion, fundamentally a cell-survival system to resist various environmental stresses, including nutrient deprivation, hypoxia and cytotoxic agents [6]. There are reports suggesting Dkk-3 involvement in the induction and inhibition of autophagy [31,32]. In the current study, it is considered that Dkk-3 knock-down induced compensatory activation of the Erk1/2 signaling pathway to survive the stress and led to the induction of autophagy or macropinocytosis according to the extracellular condition.…”

Synergistic anti‐pancreatic cancer immunological effects by treatment with reduced expression in immortalized cells/dickkopf‐3 protein and peripheral blood mononuclear cells

“…As the prognosis of pancreatic cancer is poor, new innovative therapeutic modalities need to be developed . The REIC/DKK3 gene was isolated and cloned as an immortalization‐related gene at Okayama University in 2000 and identified as a new tumor suppressor gene . REIC/DKK3 gene therapy was demonstrated to induce immunological effects, in addition to the induction of cancer cell apoptosis in a prostate cancer study .…”

“…The reduced expression in immortalized cells (REIC) gene, also called dickkopf‐3 (DKK3), was originally identified in our institution as an immortalization‐related gene . REIC/DKK3 gene expression was decreased or lost in pancreatic and other cancers, and adenovirus‐mediated REIC/DKK3 overexpression induces cancer cell death . The overexpression of the REIC/DKK3 gene induces endoplasmic reticulum stress, which is responsible for apoptosis through the c‐Jun‐NH2‐kinase pathway in cancer cells.…”