Oncolytic effect of adenoviruses serotypes 5 and 6 against U87 glioblastoma cancer stem cells

Margarita V. Romanenko, Evgeniya V. Dolgova, Ivan D. Osipov, Genrikh S. Ritter, Mariya S. Sizova, Anastasia S. Proskurina, Yaroslav R. Efremov, Sergey I. Bayborodin, Ekaterina A. Potter, Oleg S. Taranov, Vladimir V. Omigov, Galina V. Kochneva, Antonina A. Grazhdantseva, Evgeniy L. Zavyalov, Ivan A. Razumov, Sergey V. Netesov, Sergey S. Bogachev

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background/Aim: Oncolytic adenoviruses are promising therapeutic agents against both the bulk of tumor cells and cancer stem cells. The present study intended to test the oncolytic capability of adenovirus serotype 6 (Ad6), which has a lower seroprevalence and hepatotoxicity relatively to adenovirus 5 (Ad5), against the glioblastoma and its cancer stem cells. Materials and Methods: Oncolytic efficacy of Ad6 was compared to widespread Ad5 both in vitro and in vivo, using the U87 and U251 human glioblastoma cell lines and subcutaneously transplanted U87 cells in SCID mice, respectively. Results: Ad6 had a dose-dependent cytotoxicity toward glioblastoma cells in vitro and its intratumoral injections lead to a significant (p<0.05) decrease in volume of U87 xenografts, similarly to Ad5. Based on the innate capability of glioblastoma cancer stem cells to internalize a fluorescent-labeled double-stranded DNA probe, the spatial localization of these cells was estimated and it was shown that the number of cancer stem cells tended to decrease under adenovirus therapy as compared to the control group. Conclusion: Ad6 was shown to be a promising agent for treating glioblastomas.

Original languageEnglish (US)
Pages (from-to)6073-6086
Number of pages14
JournalAnticancer Research
Volume39
Issue number11
DOIs
StatePublished - 2019
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the State Project of the Institute of Cytology and Genetics # 0324-2019-0042, State Project #6.5546.2017 of Novosibirsk State University, top-100 Program Funding of the same University and the grant #18-34-20016 of the Russian Foundation for Basic Research.

Keywords

  • Cancer stem cells
  • DNA internalization
  • TAMRA
  • U87 cell line
  • Аdenovirus

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