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Omeljaniuk WJ, Krętowski R, Ratajczak-Wrona W, et al. Novel Dual PI3K/mTOR Inhibitor, Apitolisib (GDC-0980), Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells. Int J Mol Sci. 2021;22(21)doi: 10.3390/ijms222111511.
Omeljaniuk, W. J., Krętowski, R., Ratajczak-Wrona, W., Jabłońska, E., & Cechowska-Pasko, M. (2021). Novel Dual PI3K/mTOR Inhibitor, Apitolisib (GDC-0980), Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells. International journal of molecular sciences, 22(21), . https://doi.org/10.3390/ijms222111511
Omeljaniuk, Wioleta Justyna, et al. "Novel Dual PI3K/mTOR Inhibitor, Apitolisib (GDC-0980), Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells." International journal of molecular sciences vol. 22,21 (2021). doi: https://doi.org/10.3390/ijms222111511
Omeljaniuk WJ, Krętowski R, Ratajczak-Wrona W, Jabłońska E, Cechowska-Pasko M. Novel Dual PI3K/mTOR Inhibitor, Apitolisib (GDC-0980), Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells. Int J Mol Sci. 2021 Oct 26;22(21). doi: 10.3390/ijms222111511. PMID: 34768941; PMCID: PMC8583746.
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Int J Mol Sci. 2021 Oct 26;22(21). doi: 10.3390/ijms222111511.

Novel Dual PI3K/mTOR Inhibitor, Apitolisib (GDC-0980), Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells.

International journal of molecular sciences

Wioleta Justyna Omeljaniuk, Rafał Krętowski, Wioletta Ratajczak-Wrona, Ewa Jabłońska, Marzanna Cechowska-Pasko

Affiliations

  1. Department of Pharmaceutical Biochemistry, Medical University of Bialystok, 15-222 Bialystok, Poland.
  2. Department of Immunology, Medical University of Bialystok, 15-269 Bialystok, Poland.

PMID: 34768941 PMCID: PMC8583746 DOI: 10.3390/ijms222111511

Abstract

Deregulated PI3K/AKT/mTOR signalling commonly exists in glioblastoma, making this axis an attractive target for therapeutic manipulation. Given that activation of PI3K/AKT/mTOR promotes tumour growth, metastasis, and resistance to anticancer therapies, mTOR inhibitors show promise in the treatment of cancer. The aim of this study was to investigate the underlying mechanism of novel dual PI3K/mTOR inhibitor, Apitolisib (GDC-0980), in A-172 and U-118-MG GBM tumour cell line suppression. It has been demonstrated that GDC-0980 induces time- and dose-dependent cytotoxicity and apoptosis in investigated glioma cell lines. In our study, the strongest induction of apoptosis was exhibited in the A-172 line after 48 h of incubation with 20 µM GDC-0980, where we observed 46.47% of apoptotic cells. In conclusion, we first discovered that dual PI3K/mTOR blockade by GDC-0980 markedly suppressed survival of human GBM cells and induced apoptosis, independent of the ER stress-mediated DR5 activation. We suggest that GDC-0980, by exerting an inhibitory effect on PERK expression, may thus block its inhibitory effect on protein synthesis, leading to intensification of translation, and this may result in an increase in apoptosis. On the other hand, CHOP stimulates protein synthesis and increases apoptosis. These findings suggest that GDC-0980 may be a candidate for further evaluation as a chemotherapeutic agent for anti-GBM therapy.

Keywords: GDC-0980; apitolisib; apoptosis; dual PI3K/mTOR inhibitor; glioblastoma

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