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- W1941036222 abstract "Tyrosine kinase inhibitors (TKIs) including axitinib have been introduced in the treatment of renal cell carcinoma (RCC) because of their anti-angiogenic properties. However, no evidence are presently available on a direct cytotoxic anti-tumor activity of axitinib in RCC.Herein we reported by western blot analysis that axitinib treatment induces a DNA damage response (DDR) initially characterized by γ-H2AX phosphorylation and Chk1 kinase activation and at later time points by p21 overexpression in A-498 and Caki-2 RCC cells although with a different potency. Analysis by immunocytochemistry for the presence of 8-oxo-7,8-dihydro-2'-deoxyguanosine in cellular DNA and flow cytometry using the redox-sensitive fluorescent dye DCFDA, demonstrated that DDR response is accompanied by the presence of oxidative DNA damage and reactive oxygen species (ROS) generation. This response leads to G2/M cell cycle arrest and induces a senescent-like phenotype accompanied by enlargement of cells and increased senescence-associated β-galactosidase activity, which are abrogated by N-acetyl cysteine (NAC) pre-treatment. In addition, axitinib-treated cells undergo to cell death through mitotic catastrophe characterized by micronucleation and abnormal microtubule assembly as assessed by fluorescence microscopy.On the other hand, axitinib, through the DDR induction, is also able to increase the surface NKG2D ligand expression. Accordingly, drug treatment promotes NK cell recognition and degranulation in A-498 RCC cells in a ROS-dependent manner.Collectively, our results indicate that both cytotoxic and immunomodulatory effects on RCC cells can contribute to axitinib anti-tumor activity." @default.
- W1941036222 created "2016-06-24" @default.
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- W1941036222 date "2015-10-14" @default.
- W1941036222 modified "2023-10-11" @default.
- W1941036222 title "Axitinib induces DNA damage response leading to senescence, mitotic catastrophe, and increased NK cell recognition in human renal carcinoma cells" @default.
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- W1941036222 cites W1797447800 @default.
- W1941036222 cites W1873584279 @default.
- W1941036222 cites W1930421942 @default.
- W1941036222 cites W1964609719 @default.
- W1941036222 cites W1965239527 @default.
- W1941036222 cites W1965688832 @default.
- W1941036222 cites W1968291992 @default.
- W1941036222 cites W1970863720 @default.
- W1941036222 cites W1971476329 @default.
- W1941036222 cites W1980863092 @default.
- W1941036222 cites W1980878904 @default.
- W1941036222 cites W1985775217 @default.
- W1941036222 cites W1991037989 @default.
- W1941036222 cites W1995642740 @default.
- W1941036222 cites W1999191024 @default.
- W1941036222 cites W1999966467 @default.
- W1941036222 cites W2007825988 @default.
- W1941036222 cites W2009891171 @default.
- W1941036222 cites W2010895845 @default.
- W1941036222 cites W2016599680 @default.
- W1941036222 cites W2023942118 @default.
- W1941036222 cites W2023952988 @default.
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- W1941036222 cites W2035307176 @default.
- W1941036222 cites W2046319968 @default.
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- W1941036222 doi "https://doi.org/10.18632/oncotarget.5768" @default.
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