The role of CIP2A as a therapeutic target of rapamycin in radioresistant head and neck cancer with TP53 mutation
Song Hee Kim PhD Won Hyeok Lee PhD Daseul Seong Jae Hee An Hyoung Uk Je MD Hae Yun Nam PhD Sang Yoon Kim MD, PhD Seong Who Kim MD, PhD Myung Woul Han MD, PhD
First published: 03 July 2019 https://doi.org/10.1002/hed.25868
Funding information: National Research Foundation of Korea, Grant/Award Number: NRF‐2013R1A1A3010109, NRF‐2016R1D1A1B03934833, NRF‐2019R1A2C1006788
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Abstract
Background
CIP2A may activate multiple oncogenic proteins and promote the proliferation of various cancer cells.
Methods
We investigated that the role of CIP2A in radioresistant head and neck cancer (HNC) cell line with TP53 mutation and the effect of the rapamycin on the response of HN31 with TP53 mutation cells to irradiation related to CIP2A expression.
Results
CIP2A expression was stimulated by p53 mutation and critical for the inhibition of senescence induction in response to radiation. The treatment with radiation alone neither induced cytotoxicity in HN31 cells nor completely suppressed the activation of CIP2A. However, the combination of radiation and rapamycin increase the radiosensitivity through the induction of senescence with downregulation of CIP2A expression both in vivo and in vitro.
Conclusion
Our results suggest that CIP2A may serve as a therapeutic target of rapamycin through induction of senescence in radioresistant HNC with TP53 mutation.
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