THE СYTOTOXIC EFFECTS OF NERVE GROWTH FACTOR AND ITS COMBINATIONS WITH CHEMOTHERAPEUTIC DRUGS ON ANAPLASTIC ASTROCYTOMA, GLIOBLASTOMA AND MEDUBLOBLASTOMA CELLS IN VITRO



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Abstract

Abstract. Currently, the effectiveness of the treatment of malignant tumors using surgical resection, radiotherapy and chemotherapy is insufficient. Therefore, new research is needed to find alternative molecules with antitumor effects. It is known that nerve growth factor (NGF) inhibits invasion, migration, and angiogenesis of tumor cells. Studying the effects of NGF on brain tumors, as well as its combinations with chemotherapy drugs used in medicine, may contribute to the development of new treatment regimens for malignant neoplasms in the central nervous system. The purpose of this study is an exploration the molecular and cellular mechanisms of antitumor effects of individual and combined preparations of NGF and chemotherapeutic drugs on brain tumor cells (gliomas C6, U251, anaplastic astrocytoma, glioblastoma and medulloblastoma).

Materials and methods. The study was performed on glioma cell lines rat C6, human U251, as well as on primary cells of anaplastic astrocytoma (AA, n=9), glioblastoma (GBM, n=9) and medulloblastoma (MB, n=38) patients. The cytotoxicity of chemotherapeutic drugs, NGF and their combinations against tumor cells was assessed using the MTT test. The expression of TrkA and p75 receptors on AA, GBM and MB cells was assessed by immunofluorescence analysis using anti-TrkA and anti-p75 monoclonal antibodies.

Results. NGF exhibits in vitro cytotoxic activity that exceeds the activity of chemotherapy drugs towards rat glioma C6, human U251, AA, GBM and MB cells. The cytotoxic activity of NGF in combination with chemotherapy drugs is significantly higher than the activity of the individual NGF drug against MB cells, while against AA cells it is comparable to the indicators of the isolated action of NGF, and lower for GBM cells. The effectiveness of the cytotoxic effect of the combinations NGF + cisplatin and NGF + temozolomide on AA and GBM cells correlates with both the expression of TrkA receptors, p75, and their coexpression, indicating that expression indicators can be considered as markers of tumor cell sensitivity to NGF

Conclusions. The data obtained allow us to consider NGF as a potential antitumor drug for the treatment of brain tumors. Thus, NGF can act as a potential antitumor drug for the development of new treatment regimens for brain tumors.

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About the authors

Alexander Chernov

Institute of Experimental Medicine

Email: al.chernov@mail.ru

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

Russian Federation

Elvira S Galimova

1FSBSI "Institute of Experimental Medicine", Saint-Petersburg, Russia;
2Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint-Petersburg, Russia;

Author for correspondence.
Email: elvira8galimova@gmail.com

старший научный сотрудник, к.б.н.

Russian Federation

Olga V Shamova

1FSBSI "Institute of Experimental Medicine", Saint-Petersburg, Russia;

Email: oshamova@yandex.ru

заведующая отделом общей патологии и патофизиологии, доктор биологических наук, доцент, член-корреспондент РАН

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