LY294002 and sorafenib as inhibitors of intracellular survival pathways in the elimination of human glioma cells by programmed cell death.
Apoptosis
Autophagy
Gliomas
LY294002
Sorafenib
Journal
Cell and tissue research
ISSN: 1432-0878
Titre abrégé: Cell Tissue Res
Pays: Germany
ID NLM: 0417625
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
received:
21
01
2021
accepted:
02
06
2021
pubmed:
9
7
2021
medline:
9
2
2022
entrez:
8
7
2021
Statut:
ppublish
Résumé
Gliomas are aggressive brain tumors with very high resistance to chemotherapy throughout the overexpression of multiple intracellular survival pathways. Therefore, the aim of the present study was to investigate for the first time the anticancer activity of LY294002, phosphatidylinositol 3-kinase (PI3K) inhibitor and sorafenib, and rapidly accelerated fibrosarcoma kinase (Raf) inhibitor in the elimination of human glioma cells by programmed cell death. MOGGCCM (anaplastic astrocytoma, III) and T98G (glioblastoma multiforme, IV) cell lines incubated with LY294002 and/or sorafenib were used in the experiments. Simultaneous treatment with both drugs was more effective in the elimination of cancer cells on the way of apoptosis with no significant necrotic effect than single application. It was correlated with decreasing the mitochondrial membrane potential and activation of caspase 3 and 9. The expression of Raf and PI3K was also inhibited. Blocking of those kinases expression by specific siRNA revealed significant apoptosis induction, exceeding the level observed after LY294002 and sorafenib treatment in non-transfected lines but only in MOGGCCM cells. Our results indicated that combination of LY294002 and sorafenib was very efficient in apoptosis induction in glioma cells. Anaplastic astrocytoma cells turned out to be more sensitive for apoptosis induction than glioblastoma multiforme after blocking PI3K and Raf expression with siRNA.
Identifiants
pubmed: 34236519
doi: 10.1007/s00441-021-03481-0
pii: 10.1007/s00441-021-03481-0
pmc: PMC8526469
doi:
Substances chimiques
Chromones
0
Morpholines
0
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
31M2U1DVID
Sorafenib
9ZOQ3TZI87
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
17-28Informations de copyright
© 2021. The Author(s).
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