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Mol. Cells 2013; 36(4): 347-354

Published online October 31, 2013

https://doi.org/10.1007/s10059-013-0153-3

© The Korean Society for Molecular and Cellular Biology

Anticancer Effects of the Engineered Stem Cells Transduced with Therapeutic Genes via a Selective Tumor Tropism Caused by Vascular Endothelial Growth Factor Toward HeLa Cervical Cancer Cells

Hye-Sun Kim, Bo-Rim Yi, Kyung-A Hwang, Seung U. Kim, and Kyung-Chul Choi

1Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Korea, 2Medical Research Institute, Chung-Ang University College of Medicine, Seoul 156-756, Korea, 3These authors contributed equally to this work.

Received: May 14, 2013; Revised: July 22, 2013; Accepted: July 23, 2013

Abstract

The aim of the present study was to investigate the therapeutic efficacy of genetically engineered stem cells (GESTECs) expressing bacterial cytosine deaminase (CD) and/ or human interferon-beta (IFN-?) gene against HeLa cervical cancer and the migration factors of the GESTECs toward the cancer cells. Anticancer effect of GESTECs was examined in a co-culture with HeLa cells using MTT assay to measure cell viability. A transwell migration assay was performed so as to assess the migration capability of the stem cells to cervical cancer cells. Next, several che-moattractant ligands and their receptors related to a selective migration of the stem cells toward HeLa cells were determined by real-time PCR. The cell viability of HeLa cells was decreased in response to 5-fluorocytosine (5-FC), a prodrug, indicating that 5-fluorouracil (5-FU), a toxic metabolite, was converted from 5-FC by CD gene and it caused the cell death in a co-culture system. When IFN-β was additionally expressed with CD gene by these GESTECs, the anticancer activity was significantly increased. In the migration assay, the GESTECs selectively migrated to HeLa cervical cancer cells. As results of real-time PCR, chemoattractant ligands such as MCP-1, SCF, and VEGF were expressed in HeLa cells, and several receptors such as uPAR, VEGFR2, and c-kit were produced by the GES-TECs. These GESTECs transduced with CD gene and IFN-? may provide a potential of a novel gene therapy for anti-cervical cancer treatments via their selective tumor tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTECs.

Keywords cervical cancer, cytosine deaminase, GESTECs, interferon-beta, VEGF

Article

Research Article

Mol. Cells 2013; 36(4): 347-354

Published online October 31, 2013 https://doi.org/10.1007/s10059-013-0153-3

Copyright © The Korean Society for Molecular and Cellular Biology.

Anticancer Effects of the Engineered Stem Cells Transduced with Therapeutic Genes via a Selective Tumor Tropism Caused by Vascular Endothelial Growth Factor Toward HeLa Cervical Cancer Cells

Hye-Sun Kim, Bo-Rim Yi, Kyung-A Hwang, Seung U. Kim, and Kyung-Chul Choi

1Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Korea, 2Medical Research Institute, Chung-Ang University College of Medicine, Seoul 156-756, Korea, 3These authors contributed equally to this work.

Received: May 14, 2013; Revised: July 22, 2013; Accepted: July 23, 2013

Abstract

The aim of the present study was to investigate the therapeutic efficacy of genetically engineered stem cells (GESTECs) expressing bacterial cytosine deaminase (CD) and/ or human interferon-beta (IFN-?) gene against HeLa cervical cancer and the migration factors of the GESTECs toward the cancer cells. Anticancer effect of GESTECs was examined in a co-culture with HeLa cells using MTT assay to measure cell viability. A transwell migration assay was performed so as to assess the migration capability of the stem cells to cervical cancer cells. Next, several che-moattractant ligands and their receptors related to a selective migration of the stem cells toward HeLa cells were determined by real-time PCR. The cell viability of HeLa cells was decreased in response to 5-fluorocytosine (5-FC), a prodrug, indicating that 5-fluorouracil (5-FU), a toxic metabolite, was converted from 5-FC by CD gene and it caused the cell death in a co-culture system. When IFN-β was additionally expressed with CD gene by these GESTECs, the anticancer activity was significantly increased. In the migration assay, the GESTECs selectively migrated to HeLa cervical cancer cells. As results of real-time PCR, chemoattractant ligands such as MCP-1, SCF, and VEGF were expressed in HeLa cells, and several receptors such as uPAR, VEGFR2, and c-kit were produced by the GES-TECs. These GESTECs transduced with CD gene and IFN-? may provide a potential of a novel gene therapy for anti-cervical cancer treatments via their selective tumor tropism derived from VEGF and VEGFR2 expressions between HeLa cells and the GESTECs.

Keywords: cervical cancer, cytosine deaminase, GESTECs, interferon-beta, VEGF

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

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