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Antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo

BACKGROUND: The incidence of colorectal cancer (CRC) is on the rise. Furthermore, late-stage diagnoses and limited efficacious treatment options make CRC a complex clinical challenge. Therefore, a new therapeutic regimen with a completely novel therapeutic mechanism is necessary for CRC. In the pres...

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Autores principales: Yin, Lei, Zhao, Chunhong, Han, Jixia, Li, Zengjun, Zhen, Yanan, Xiao, Ruixue, Xu, Zhongfa, Sun, Yanlai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308569/
https://www.ncbi.nlm.nih.gov/pubmed/28223815
http://dx.doi.org/10.2147/TCRM.S128575
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author Yin, Lei
Zhao, Chunhong
Han, Jixia
Li, Zengjun
Zhen, Yanan
Xiao, Ruixue
Xu, Zhongfa
Sun, Yanlai
author_facet Yin, Lei
Zhao, Chunhong
Han, Jixia
Li, Zengjun
Zhen, Yanan
Xiao, Ruixue
Xu, Zhongfa
Sun, Yanlai
author_sort Yin, Lei
collection PubMed
description BACKGROUND: The incidence of colorectal cancer (CRC) is on the rise. Furthermore, late-stage diagnoses and limited efficacious treatment options make CRC a complex clinical challenge. Therefore, a new therapeutic regimen with a completely novel therapeutic mechanism is necessary for CRC. In the present study, the therapeutic efficacy of oncolytic herpes simplex virus type 2 (oHSV2) in CRC was assessed in vitro and in vivo. oHSV2 is an oncolytic agent derived from herpes simplex virus type 2 that encodes granulocyte-macrophage colony-stimulating factor. MATERIALS AND METHODS: We investigated the cytopathic effects of oHSV2 in CRC cell lines using the MTT assay. Then, cell cycle progression and apoptosis of oHSV2 were examined by flow cytometry. We generated a model of CRC with mouse CRC cell CT26 in BALB/c mice. The antitumor effects and adaptive immune response of oHSV2 were assessed in tumor-bearing mice. The therapeutic efficacy of oHSV2 was compared with the traditional chemotherapeutic agent, 5-fluorouracil. RESULTS: The in vitro data showed that oHSV2 infected the CRC cell lines successfully and that the tumor cells formed a significant number of syncytiae postinfection. The oHSV2 killed cancer cells independent of the cell cycle and mainly caused tumor cells necrosis. The in vivo results showed that oHSV2 significantly inhibited tumor growth and prolonged survival of tumor-bearing mice without weight loss. With virus replication, oHSV2 not only resulted in a reduction of myeloid-derived suppressor cells and regulatory T cells in the spleen, but also increased the number of mature dendritic cells in tumor-draining lymph nodes and the effective CD4(+)T and CD8(+)T-cells in the tumor microenvironment. CONCLUSION: Our study provides the first evidence that oHSV2 induces cell death in CRC in vitro and in vivo. These findings indicate that oHSV2 is an effective therapeutic cancer candidate that causes an oncolytic effect and recruits adaptive immune responses for an enhanced therapeutic impact, thus providing a potential therapeutic tool for treatment of CRC.
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spelling pubmed-53085692017-02-21 Antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo Yin, Lei Zhao, Chunhong Han, Jixia Li, Zengjun Zhen, Yanan Xiao, Ruixue Xu, Zhongfa Sun, Yanlai Ther Clin Risk Manag Original Research BACKGROUND: The incidence of colorectal cancer (CRC) is on the rise. Furthermore, late-stage diagnoses and limited efficacious treatment options make CRC a complex clinical challenge. Therefore, a new therapeutic regimen with a completely novel therapeutic mechanism is necessary for CRC. In the present study, the therapeutic efficacy of oncolytic herpes simplex virus type 2 (oHSV2) in CRC was assessed in vitro and in vivo. oHSV2 is an oncolytic agent derived from herpes simplex virus type 2 that encodes granulocyte-macrophage colony-stimulating factor. MATERIALS AND METHODS: We investigated the cytopathic effects of oHSV2 in CRC cell lines using the MTT assay. Then, cell cycle progression and apoptosis of oHSV2 were examined by flow cytometry. We generated a model of CRC with mouse CRC cell CT26 in BALB/c mice. The antitumor effects and adaptive immune response of oHSV2 were assessed in tumor-bearing mice. The therapeutic efficacy of oHSV2 was compared with the traditional chemotherapeutic agent, 5-fluorouracil. RESULTS: The in vitro data showed that oHSV2 infected the CRC cell lines successfully and that the tumor cells formed a significant number of syncytiae postinfection. The oHSV2 killed cancer cells independent of the cell cycle and mainly caused tumor cells necrosis. The in vivo results showed that oHSV2 significantly inhibited tumor growth and prolonged survival of tumor-bearing mice without weight loss. With virus replication, oHSV2 not only resulted in a reduction of myeloid-derived suppressor cells and regulatory T cells in the spleen, but also increased the number of mature dendritic cells in tumor-draining lymph nodes and the effective CD4(+)T and CD8(+)T-cells in the tumor microenvironment. CONCLUSION: Our study provides the first evidence that oHSV2 induces cell death in CRC in vitro and in vivo. These findings indicate that oHSV2 is an effective therapeutic cancer candidate that causes an oncolytic effect and recruits adaptive immune responses for an enhanced therapeutic impact, thus providing a potential therapeutic tool for treatment of CRC. Dove Medical Press 2017-02-07 /pmc/articles/PMC5308569/ /pubmed/28223815 http://dx.doi.org/10.2147/TCRM.S128575 Text en © 2017 Yin et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Yin, Lei
Zhao, Chunhong
Han, Jixia
Li, Zengjun
Zhen, Yanan
Xiao, Ruixue
Xu, Zhongfa
Sun, Yanlai
Antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo
title Antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo
title_full Antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo
title_fullStr Antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo
title_full_unstemmed Antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo
title_short Antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo
title_sort antitumor effects of oncolytic herpes simplex virus type 2 against colorectal cancer in vitro and in vivo
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308569/
https://www.ncbi.nlm.nih.gov/pubmed/28223815
http://dx.doi.org/10.2147/TCRM.S128575
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