Efficient virotherapy for osteosarcoma by telomerase-specific oncolytic adenovirus

Guidong Li, Hiroyuki Kawashima, Akira Ogose, Takashi Ariizumi, Yongjun Xu, Tetsuo Hotta, Yasuo Urata, Toshiyoshi Fujiwara, Naoto Endo

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Purpose: A telomerase-specific oncolytic adenovirus, Telomelysin, can selectively kill cancer cells, and be attenuated in normal cells. We herein describe the oncolytic effect of Telomelysin on human osteosarcoma both in vitro and in vivo. Methods: The anti-tumor effects of Telomelysin were evaluated on human osteosarcoma cell lines in vitro and in a mouse xenograft model of human osteosarcoma in vivo. The replication efficiencies of Telomelysin in human osteosarcoma cell lines and normal cell lines and in osteosarcoma xenografts were determined by the expression levels of E1 mRNA and E1A protein using real-time quantitative PCR, Western blot analysis and immunohistochemistry. The in vitro telomerase-specific replication and the viral infection rate were also confirmed by TelomeScan (Telomelysin-GFP), using fluorescent microscopy and flow cytometry, respectively. The cell viabilities were examined by XTT assay, and the tumor volumes were measured every 2 days. The induction of apoptosis was assessed by Western blot analysis, as well as by TUNEL assay. Results: TelomeScan and Telomelysin were efficiently replicated in human osteosarcoma cell lines and led to a dose- and time-dependent expression of GFP, E1 mRNA and E1A protein. Telomelysin infection induced marked cytolysis and apoptosis in osteosarcoma cell lines in vitro. Neither cytotoxicity nor apoptosis were induced in normal human cell lines. In the human osteosarcoma cell xenograft model, intratumoral injection of Telomelysin resulted in increased viral replication, significant tumor growth suppression and distinct apoptotic cell death. Conclusions: This study indicated that virotherapy with Telomelysin may provide a promising strategy for the treatment of human osteosarcoma.

Original languageEnglish
Pages (from-to)1037-1051
Number of pages15
JournalJournal of Cancer Research and Clinical Oncology
Volume137
Issue number6
DOIs
Publication statusPublished - Jun 2011

Fingerprint

Telomerase
Osteosarcoma
Adenoviridae
Cell Line
Heterografts
Apoptosis
Western Blotting
Neoplasms
Messenger RNA
In Situ Nick-End Labeling
Virus Diseases
Tumor Burden
Real-Time Polymerase Chain Reaction
Microscopy
Cell Survival
Flow Cytometry
Proteins
Cell Death
Immunohistochemistry
Injections

Keywords

  • Apoptosis
  • Oncolytic adenovirus
  • Osteosarcoma
  • Telomerase
  • Virotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Efficient virotherapy for osteosarcoma by telomerase-specific oncolytic adenovirus. / Li, Guidong; Kawashima, Hiroyuki; Ogose, Akira; Ariizumi, Takashi; Xu, Yongjun; Hotta, Tetsuo; Urata, Yasuo; Fujiwara, Toshiyoshi; Endo, Naoto.

In: Journal of Cancer Research and Clinical Oncology, Vol. 137, No. 6, 06.2011, p. 1037-1051.

Research output: Contribution to journalArticle

Li, G, Kawashima, H, Ogose, A, Ariizumi, T, Xu, Y, Hotta, T, Urata, Y, Fujiwara, T & Endo, N 2011, 'Efficient virotherapy for osteosarcoma by telomerase-specific oncolytic adenovirus', Journal of Cancer Research and Clinical Oncology, vol. 137, no. 6, pp. 1037-1051. https://doi.org/10.1007/s00432-010-0969-6
Li, Guidong ; Kawashima, Hiroyuki ; Ogose, Akira ; Ariizumi, Takashi ; Xu, Yongjun ; Hotta, Tetsuo ; Urata, Yasuo ; Fujiwara, Toshiyoshi ; Endo, Naoto. / Efficient virotherapy for osteosarcoma by telomerase-specific oncolytic adenovirus. In: Journal of Cancer Research and Clinical Oncology. 2011 ; Vol. 137, No. 6. pp. 1037-1051.
@article{fec0a53d150d41bd99ab31cc9ede3597,
title = "Efficient virotherapy for osteosarcoma by telomerase-specific oncolytic adenovirus",
abstract = "Purpose: A telomerase-specific oncolytic adenovirus, Telomelysin, can selectively kill cancer cells, and be attenuated in normal cells. We herein describe the oncolytic effect of Telomelysin on human osteosarcoma both in vitro and in vivo. Methods: The anti-tumor effects of Telomelysin were evaluated on human osteosarcoma cell lines in vitro and in a mouse xenograft model of human osteosarcoma in vivo. The replication efficiencies of Telomelysin in human osteosarcoma cell lines and normal cell lines and in osteosarcoma xenografts were determined by the expression levels of E1 mRNA and E1A protein using real-time quantitative PCR, Western blot analysis and immunohistochemistry. The in vitro telomerase-specific replication and the viral infection rate were also confirmed by TelomeScan (Telomelysin-GFP), using fluorescent microscopy and flow cytometry, respectively. The cell viabilities were examined by XTT assay, and the tumor volumes were measured every 2 days. The induction of apoptosis was assessed by Western blot analysis, as well as by TUNEL assay. Results: TelomeScan and Telomelysin were efficiently replicated in human osteosarcoma cell lines and led to a dose- and time-dependent expression of GFP, E1 mRNA and E1A protein. Telomelysin infection induced marked cytolysis and apoptosis in osteosarcoma cell lines in vitro. Neither cytotoxicity nor apoptosis were induced in normal human cell lines. In the human osteosarcoma cell xenograft model, intratumoral injection of Telomelysin resulted in increased viral replication, significant tumor growth suppression and distinct apoptotic cell death. Conclusions: This study indicated that virotherapy with Telomelysin may provide a promising strategy for the treatment of human osteosarcoma.",
keywords = "Apoptosis, Oncolytic adenovirus, Osteosarcoma, Telomerase, Virotherapy",
author = "Guidong Li and Hiroyuki Kawashima and Akira Ogose and Takashi Ariizumi and Yongjun Xu and Tetsuo Hotta and Yasuo Urata and Toshiyoshi Fujiwara and Naoto Endo",
year = "2011",
month = "6",
doi = "10.1007/s00432-010-0969-6",
language = "English",
volume = "137",
pages = "1037--1051",
journal = "Journal of Cancer Research and Clinical Oncology",
issn = "0171-5216",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - Efficient virotherapy for osteosarcoma by telomerase-specific oncolytic adenovirus

AU - Li, Guidong

AU - Kawashima, Hiroyuki

AU - Ogose, Akira

AU - Ariizumi, Takashi

AU - Xu, Yongjun

AU - Hotta, Tetsuo

AU - Urata, Yasuo

AU - Fujiwara, Toshiyoshi

AU - Endo, Naoto

PY - 2011/6

Y1 - 2011/6

N2 - Purpose: A telomerase-specific oncolytic adenovirus, Telomelysin, can selectively kill cancer cells, and be attenuated in normal cells. We herein describe the oncolytic effect of Telomelysin on human osteosarcoma both in vitro and in vivo. Methods: The anti-tumor effects of Telomelysin were evaluated on human osteosarcoma cell lines in vitro and in a mouse xenograft model of human osteosarcoma in vivo. The replication efficiencies of Telomelysin in human osteosarcoma cell lines and normal cell lines and in osteosarcoma xenografts were determined by the expression levels of E1 mRNA and E1A protein using real-time quantitative PCR, Western blot analysis and immunohistochemistry. The in vitro telomerase-specific replication and the viral infection rate were also confirmed by TelomeScan (Telomelysin-GFP), using fluorescent microscopy and flow cytometry, respectively. The cell viabilities were examined by XTT assay, and the tumor volumes were measured every 2 days. The induction of apoptosis was assessed by Western blot analysis, as well as by TUNEL assay. Results: TelomeScan and Telomelysin were efficiently replicated in human osteosarcoma cell lines and led to a dose- and time-dependent expression of GFP, E1 mRNA and E1A protein. Telomelysin infection induced marked cytolysis and apoptosis in osteosarcoma cell lines in vitro. Neither cytotoxicity nor apoptosis were induced in normal human cell lines. In the human osteosarcoma cell xenograft model, intratumoral injection of Telomelysin resulted in increased viral replication, significant tumor growth suppression and distinct apoptotic cell death. Conclusions: This study indicated that virotherapy with Telomelysin may provide a promising strategy for the treatment of human osteosarcoma.

AB - Purpose: A telomerase-specific oncolytic adenovirus, Telomelysin, can selectively kill cancer cells, and be attenuated in normal cells. We herein describe the oncolytic effect of Telomelysin on human osteosarcoma both in vitro and in vivo. Methods: The anti-tumor effects of Telomelysin were evaluated on human osteosarcoma cell lines in vitro and in a mouse xenograft model of human osteosarcoma in vivo. The replication efficiencies of Telomelysin in human osteosarcoma cell lines and normal cell lines and in osteosarcoma xenografts were determined by the expression levels of E1 mRNA and E1A protein using real-time quantitative PCR, Western blot analysis and immunohistochemistry. The in vitro telomerase-specific replication and the viral infection rate were also confirmed by TelomeScan (Telomelysin-GFP), using fluorescent microscopy and flow cytometry, respectively. The cell viabilities were examined by XTT assay, and the tumor volumes were measured every 2 days. The induction of apoptosis was assessed by Western blot analysis, as well as by TUNEL assay. Results: TelomeScan and Telomelysin were efficiently replicated in human osteosarcoma cell lines and led to a dose- and time-dependent expression of GFP, E1 mRNA and E1A protein. Telomelysin infection induced marked cytolysis and apoptosis in osteosarcoma cell lines in vitro. Neither cytotoxicity nor apoptosis were induced in normal human cell lines. In the human osteosarcoma cell xenograft model, intratumoral injection of Telomelysin resulted in increased viral replication, significant tumor growth suppression and distinct apoptotic cell death. Conclusions: This study indicated that virotherapy with Telomelysin may provide a promising strategy for the treatment of human osteosarcoma.

KW - Apoptosis

KW - Oncolytic adenovirus

KW - Osteosarcoma

KW - Telomerase

KW - Virotherapy

UR - http://www.scopus.com/inward/record.url?scp=79959770652&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959770652&partnerID=8YFLogxK

U2 - 10.1007/s00432-010-0969-6

DO - 10.1007/s00432-010-0969-6

M3 - Article

C2 - 21193997

AN - SCOPUS:79959770652

VL - 137

SP - 1037

EP - 1051

JO - Journal of Cancer Research and Clinical Oncology

JF - Journal of Cancer Research and Clinical Oncology

SN - 0171-5216

IS - 6

ER -