NERVE GROWTH FACTOR INHIBITS MIGRATION, CLONOGENICITY, AND BIOENERGETIC METABOLISM OF MITOCHONDRIA OF GLIOMA U251 CELLS

  • Authors: Chernov A.1, Glushakov R.I.1, Landynya S.S2, Sharapov Y.А3,4, Galimova E.S3,5, Shamova O.V.3,4
  • Affiliations:
    1. Institute of Experimental Medicine
    2. Институт экспериментальной медицины, Санкт-Петербург, Россия Санкт-Петербургский государственный университет, Санкт-Петербург, Россия
    3. Институт экспериментальной медицины, Санкт-Петербург, Россия
    4. Санкт-Петербургский государственный университет, Санкт-Петербург, Россия
    5. Институт эволюционной физиологии и биохимии им. И.М. Сеченова РАН, Санкт-Петербург, Россия
  • Section: Original research
  • Published: 18.07.2024
  • URL: https://journals.eco-vector.com/MAJ/article/view/632885
  • DOI: https://doi.org/10.17816/MAJ632885
  • ID: 632885


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Abstract

Introduction. Glioblastoma (GBM) is the most malignant tumor of the central nervous system. Temozolomide is the standard treatment for gliomas, and its use often leads to drug resistance and relapse of GBM. Therefore, further research is needed to find other drugs that can improve the effectiveness of standard treatments.

The goal is to study the effects of nerve growth factor, temozolomide on clonogenicity, migration and energy metabolism of mitochondria of human U251 glioma cells.

Materials and methods. The study was conducted on human U251 glioma cells. A colony formation test was used to evaluate the ability of glioma cells to form colonies in vitro. Migration of U251 glioma cells was assessed by the Scratch Assay. To study mitochondrial metabolism in glioma cells, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured using the Seahorse XF CellMito and Seahorse XF Glycolysis Stress Test kits, respectively.

Results. We found that NGF (7.55× 10-3 µM) and TMZ (155 µM) inhibited the clonogenicity of U251 glioma cells by 66.2% and 73.5–81.3% within 1–2 days, respectively. Exposure to NGF (7.55×10-3 µM) also suppresses U251 glioma cell migration on days 3 and 4. TMZ (155 µM) inhibits glioma cell migration on days 1–3. The anti-clonogenic and anti-migratory activities of NGF and TMZ may be associated with their ability to reduce the basal rate of oxygen consumption, inhibit ATP synthetase and maximum mitochondrial respiration in human U251 glioma cells. NGF and TMZ did not affect glycolysis, glycolytic capacity, and glycolytic reserve in U251 glioma cells compared to controls.

Conclusion. Thus, NGF and TMZ inhibit migration, clonogenicity, and bioenergetic metabolism of mitochondria in U251 glioma cells, exhibiting anti-mitogenic, anti-migration, and reducing energy metabolism effects.

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About the authors

Alexander Chernov

Institute of Experimental Medicine

Author for correspondence.
Email: al.chernov@mail.ru
ORCID iD: 0000-0003-2464-7370

старший научный сотрудник, к.б.н., отдела общей патологии и патологической физиологии 

Russian Federation

Ruslan Ivanovich Glushakov

Email: glushakovruslan1@gmail.com
Russian Federation

Sofia S Landynya

Институт экспериментальной медицины, Санкт-Петербург, Россия
Санкт-Петербургский государственный университет, Санкт-Петербург, Россия

Email: sofia.lanynya@mail.ru

студент, старший лаборант

Russian Federation

Yaroslav А Sharapov

Институт экспериментальной медицины, Санкт-Петербург, Россия;
Санкт-Петербургский государственный университет, Санкт-Петербург, Россия

Email: yarostloff@yandex.ru

студент, старший лаборант

Russian Federation

Elvira S Galimova

Институт экспериментальной медицины, Санкт-Петербург, Россия;
Институт эволюционной физиологии и биохимии им. И.М. Сеченова РАН, Санкт-Петербург, Россия

Email: elvira8galimova@gmail.com

старший научный сотрудник, к.б.н.

Israel

Olga Valerevna Shamova

Институт экспериментальной медицины, Санкт-Петербург, Россия;
Санкт-Петербургский государственный университет, Санкт-Петербург, Россия

Email: oshamova@yandex.ru

доктор медицинских наук, доцент, член-корреспондент РАН,

заведующий отделом общей патологии и патофизиологии

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