期刊
EXPERIMENTAL AND MOLECULAR PATHOLOGY
卷 110, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yexmp.2019.104290
关键词
Lung cancer; Carboplatin resistance; NFAT2
类别
资金
- Science and Technology Innovation Foundation [2017012152]
Carboplatin is a platinum-based chemotherapy drug in lung cancer treatment. However, its efficacy is frequently limited by intrinsic and acquired drug resistance. Recently, nucleus factor of activated T cells, cytoplasmic 1 (NFAT2) has been recognized as an oncogene and involved in disease progression and drug resistance in various cancers. In the current study, we found that overexpression of NFAT2 was associated with poor prognosis in lung cancer patients, and is observed in a carboplatin resistant lung cancer cell line, indicative of its role in regulating drug response. We further showed that NFAT2 played a critical role in promoting cell proliferation and overcome carboplatin-induced DNA damage and cell cycle arrest. NFAT2 knockdown or inhibition of its nucleus translation via cyclosporine A largely restored the sensitivity to carboplatin in the resistant line by inducing DNA damage, blocking cell cycle progression and activating apoptotic cell death. We thus suggest that NFAT2 is a putative therapeutic target to overcome carboplatin resistance in lung cancers.
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