Oral poliovirus vaccine-induced programmed cell death involves both intrinsic and extrinsic pathways in human colorectal cancer cells
Received 14 June 2018
Accepted for publication 30 August 2018
Published 30 October 2018 Volume 2018:7 Pages 95—105
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 4
Editor who approved publication: Prof. Dr. Athanasios Kyritsis
Sareh Zhand,1 Seyed Masoud Hosseini,1 Alijan Tabarraei,2 Mohsen Saeidi,2 Marie Saghaeian Jazi,3 Mohamad Reza Kalani,4 Abdolvahab Moradi2
1Department of Microbiology, Faculty of Biological Sciences and Technology, Shahid Beheshti University, Tehran, Iran; 2Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran; 3Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran; 4Department of Biochemistry, School of Molecular and Cell Biology, University of Illinois at Urbana Champaign, Urbana, IL, USA
Purpose: Colorectal cancer (CRC) is one of the most common causes of cancer death throughout the world. Replication-competent viruses, which are naturally able to infect and lyse tumor cells, seem to be promising in this field. The aim of this study was to evaluate the potential of oral poliovirus vaccine (OPV) on human CRC cells and elucidate the mechanism of apoptosis induction.
Materials and methods: Protein and gene expression of poliovirus (PV) receptor (CD155) on four human CRC cell lines including HCT116, SW480, HT-29, and Caco-2 and normal fetal human colon (FHC) cell line as a control were examined by flow cytometry and SYBR Green Real-Time PCR, respectively. Cytotoxicity of OPV on indicated cell lines was tested using MTT assay. The ability of OPV on apoptosis induction for both intrinsic and extrinsic pathways was examined using caspase-8 and caspase-9 colorimetric assay kits. The PV propagation in mentioned cell lines was investigated, and the quantity of viral yields (cells associated and extracellular) was determined using TaqMan PCR.
Results: CD155 mRNA and protein were expressed significantly higher in studied CRC cell lines rather than the normal cell line (P=0). OPV induced cell death in a time- and dose-dependent manner in human CRC cells. Apoptosis through both extrinsic and intrinsic pathways was detected in CRC cells with the minimum level found in FHC. PV viral load was significantly correlated with apoptosis via extrinsic (R=0.945, P=0.0001) and intrinsic (R=0.756, P=0.001) pathways.
Conclusion: This study suggests that OPV has potential for clinical treatment of CRC. However further studies in animal models (tumor xenografts) are needed to be certain that it is qualified enough for treatment of CRC.
Keywords: oncolytic virotherapy, oral poliovirus vaccine, colorectal cancer cells, apoptosis, CD155
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