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Volume 9, Issue 11 (Suppl)
J Cancer Sci Ther
ISSN: 1948-5956 JCST, an open access journal
Asia Pacific Oncologists 2017
November 20-22, 2017
November 20-22, 2017 Melbourne, Australia
14
th
Asia Pacific
Oncologists Annual Meeting
Antineoplastic drug NSC631570 inhibits C6 glioma growth in rats through the re-education of tumor-
associated microglia
Larysa Skivka, Mariia Rudyk, Ievgenia Opeida, Vitalina Svyatetska, Kateryna Stepura, Niccola Funel, Ascold Nowicky and Wassil Nowick
1
Taras Sevchenko National University of Kyiv, Ukraine
2
University of Pisa, Italy
3
Ukrainian Anticancer Institute, Austria
G
lioblastoma (GB) is one of the most devastating and fatal tumors. Therapeutic approaches targeting tumor cells have failed.
GB is heavily infiltrated with myeloid cells that are collectively referred to as glioma-associated microglia/macrophages
or GAM. GAM acquires the alternative, pro-invasive phenotype and creates favorable conditions for disease progression.
GAM re-education seems to be an attractive therapeutic approach to GM treatment. NSC631570 is an anticancer agent that
influences phagocyte migration and functional polarization. This study was aimed to investigate the effect of NSC631570
on C6 glioma growth in rats and microglia metabolic profile
in vitro
and
in vivo
. For tumor-associated hypoxia induction
experiments, the rat microglial cells were treated under either normoxia (21% O2) or hypoxia (3% O2) for 48 hours
in vitro
.
Intracranial drug delivery device was developed for the local treatment of glioma-bearing rats with NSC631570. Tumor-
bearing animals received seven intracranial injections of the drug at 3 days interval starting from the second day after C6 cell
transplantation. NSC631570 re-polarized hypoxic microglia to pro-inflammatory metabolic profile
in vitro
. The treatment of
tumor-bearing rats with NSC631570 was associated with prolongation of their life by 18%. This effect was accompanied by
the increase in the number of phagocytizing CD14
+
cells in the microglia fraction without the alteration in their endocytosis
intensity. The frequency of CD206
+
cells was moderately increased in the fraction of both CD14
+
and CD14-microglial cells.
Oxidative metabolism of GAM was moderately down-regulated by the drug. Intracranial introduction of the preparation was
associated with the sharp increase of NO generation by microglial cells. Locally introduced NSC631570 can re-educate GAM.
This repolarizing effect is associated with moderate tumor growth inhibition and might be considered as an important part of
the mechanism of tumor-inhibiting action of the drug.
Biography
Larysa Skivka has completed her PhD from RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine and Postdoctoral
studies from Taras Shevchenko National University of Kyiv. Currently she is a Professor of the Educational and Scientific Centre, Institute of Biology and Medicine
of Taras Shevchenko National University of Kyiv, Ukraine, Head of the Department of Microbiology and Immunology. Her area of scientific activity includes
immunomodulation as a component of adjuvant cancer therapy, functional polarization of phagocytes in the pathogenesis of inflammatory diseases.
realmed@i.com.uaLarysa Skivka et al., J Cancer Sci Ther 2017, 9:11 (Suppl)
DOI: 10.4172/1948-5956-C1-117