PARP9 knockdown confers protection against chemoresistance and immune escape of breast cancer cells by blocking the PI3K/AKT pathway
Introduction This study probes the mechanism of the PARP9/PI3K/AKT/PD-L1 axis in the chemoresistance and immune escape of breast cancer cells. Material and methods The expression of related genes was detected in MCF-7/FUL cells. After MCF-7/FUL cells were treated with sh-PARP9 and/or the PI3K/AKT p...
| Main Authors: | , , , |
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| 格式: | Article |
| 語言: | English |
| 出版: |
Termedia Publishing House
2023-03-01
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| 叢編: | Archives of Medical Science |
| 主題: | |
| 在線閱讀: | https://www.archivesofmedicalscience.com/PARP9-knockdown-confers-protection-against-chemoresistance-and-immune-escape-of-breast,161444,0,2.html |
| 總結: | Introduction
This study probes the mechanism of the PARP9/PI3K/AKT/PD-L1 axis in the chemoresistance and immune escape of breast cancer cells.
Material and methods
The expression of related genes was detected in MCF-7/FUL cells. After MCF-7/FUL cells were treated with sh-PARP9 and/or the PI3K/AKT pathway activator, drug resistance, proliferation, migration, invasion, and apoptosis were measured. Afterward, MCF-7/FUL cells were co-cultured with CD8+ T cells to examine the positive rate and density of MCF-7/FUL cells, the percentage and apoptosis of CD8+ T cells, and the expression of immune-related factors in cell supernatants. Nude mice were subcutaneously injected with sh-PARP9-transfected MCF-7/FUL cells for in vivo validation.
Results
PARP9 was highly expressed in MCF-7/FUL cells. Sh-PARP9 transfection suppressed cell migration, proliferation, and invasion while accelerating apoptosis in MCF-7/FUL cells, accompanied by downregulated PD-L1, p-PI3K, and p-AKT expression, and reduced IC50 and FUL resistance. After co-culture of MCF-7/FUL cells with CD8+ T cells, the percentage of CD8+ T cells, the expression of immune-related factors in supernatants, and the positive rate of MCF-7/FUL cells increased, while the apoptosis of CD8+ T cells and the density of adherent MCF-7/FUL cells were diminished. These trends were negated by further activating the PI3K/AKT pathway. PARP9 knockdown suppressed xenograft growth, decreased p-PI3K, p-AKT, PD-L1, and cyclin D1 expression, and augmented p-Cdc2 and cleaved caspase 3 levels in nude mice.
Conclusions
PARP9 knockdown blocked the PI3K/AKT pathway to downregulate PD-L1, thus depressing chemoresistance and immune escape in breast cancer. |
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| ISSN: | 1734-1922 1896-9151 |