Involvement of PI3K Pathway in Glioma Cell Resistance to Temozolomide Treatment
The aim of the study was to investigate the anticancer potential of LY294002 (PI3K inhibitor) and temozolomide using glioblastoma multiforme (T98G) and anaplastic astrocytoma (MOGGCCM) cells. Apoptosis, autophagy, necrosis, and granules in the cytoplasm were identified microscopically (fluorescence and electron microscopes). The mitochondrial membrane potential was studied by flow cytometry. The activity of caspases 3, 8, and 9 and Akt was evaluated fluorometrically, while the expression of Beclin 1, PI3K, Akt, mTOR, caspase 12, and Hsp27 was determined by immunoblotting. SiRNA was used to block Hsp27 and PI3K expression. Cell migration and localization of Hsp27 were tested with the wound healing assay and immunocytochemistry, respectively. LY294002 effectively diminished the migratory potential and increased programmed death of T98G and MOGGCCM. Autophagy was dominant in MOGGCCM, while apoptosis was dominant in T98G. LY294002 with temozolomide did not potentiate cell death but redirected autophagy toward apoptosis, which was correlated with ER stress. A similar effect was observed after blocking PI3K expression with siRNA. Transfection with Hsp27 siRNA significantly increased apoptosis related to ER stress. Our results indicate that inhibition of the PI3K/Akt/mTOR pathway sensitizes glioma cells to apoptosis upon temozolomide treatment, which was correlated with ER stress. Hsp27 increases the resistance of glioma cells to cell death upon temozolomide treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
International journal of molecular sciences - 22(2021), 10 vom: 13. Mai |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zając, Adrian [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.06.2021 Date Revised 10.06.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms22105155 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM326166033 |
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| 100 | 1 | |a Zając, Adrian |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Involvement of PI3K Pathway in Glioma Cell Resistance to Temozolomide Treatment |
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| 500 | |a Date Revised 10.06.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The aim of the study was to investigate the anticancer potential of LY294002 (PI3K inhibitor) and temozolomide using glioblastoma multiforme (T98G) and anaplastic astrocytoma (MOGGCCM) cells. Apoptosis, autophagy, necrosis, and granules in the cytoplasm were identified microscopically (fluorescence and electron microscopes). The mitochondrial membrane potential was studied by flow cytometry. The activity of caspases 3, 8, and 9 and Akt was evaluated fluorometrically, while the expression of Beclin 1, PI3K, Akt, mTOR, caspase 12, and Hsp27 was determined by immunoblotting. SiRNA was used to block Hsp27 and PI3K expression. Cell migration and localization of Hsp27 were tested with the wound healing assay and immunocytochemistry, respectively. LY294002 effectively diminished the migratory potential and increased programmed death of T98G and MOGGCCM. Autophagy was dominant in MOGGCCM, while apoptosis was dominant in T98G. LY294002 with temozolomide did not potentiate cell death but redirected autophagy toward apoptosis, which was correlated with ER stress. A similar effect was observed after blocking PI3K expression with siRNA. Transfection with Hsp27 siRNA significantly increased apoptosis related to ER stress. Our results indicate that inhibition of the PI3K/Akt/mTOR pathway sensitizes glioma cells to apoptosis upon temozolomide treatment, which was correlated with ER stress. Hsp27 increases the resistance of glioma cells to cell death upon temozolomide treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ER stress | |
| 650 | 4 | |a Hsp27 | |
| 650 | 4 | |a LY294002 | |
| 650 | 4 | |a gliomas | |
| 650 | 4 | |a programmed death | |
| 650 | 4 | |a temozolomide | |
| 650 | 7 | |a Antineoplastic Agents, Alkylating |2 NLM | |
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| 650 | 7 | |a Chromones |2 NLM | |
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| 650 | 7 | |a YF1K15M17Y |2 NLM | |
| 700 | 1 | |a Sumorek-Wiadro, Joanna |e verfasserin |4 aut | |
| 700 | 1 | |a Langner, Ewa |e verfasserin |4 aut | |
| 700 | 1 | |a Wertel, Iwona |e verfasserin |4 aut | |
| 700 | 1 | |a Maciejczyk, Aleksandra |e verfasserin |4 aut | |
| 700 | 1 | |a Pawlikowska-Pawlęga, Bożena |e verfasserin |4 aut | |
| 700 | 1 | |a Pawelec, Jarosław |e verfasserin |4 aut | |
| 700 | 1 | |a Wasiak, Magdalena |e verfasserin |4 aut | |
| 700 | 1 | |a Hułas-Stasiak, Monika |e verfasserin |4 aut | |
| 700 | 1 | |a Bądziul, Dorota |e verfasserin |4 aut | |
| 700 | 1 | |a Rzeski, Wojciech |e verfasserin |4 aut | |
| 700 | 1 | |a Reichert, Michał |e verfasserin |4 aut | |
| 700 | 1 | |a Jakubowicz-Gil, Joanna |e verfasserin |4 aut | |
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