Overexpression of Sphk2 is associated with gefitinib resistance in non-small cell lung cancer
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Lung cancer is the major cause of cancer-related death worldwide, and 80 % of them are non-small cell lung cancer (NSCLC) cases. Recent studies have shown that sphingosine kinase 2 (SphK2) could promote tumor progression; however, whether SphK2 could affect the chemoresistance of NSCLC to chemotherapy remains unclear. To determine whether SphK2 serves as a potential therapeutic target of NSCLC, we utilized small interference RNA (siRNA) to knock down SphK2 expression in human NSCLC cells and analyzed their phenotypic changes. The data demonstrated that knockdown of SphK2 led to decreased proliferation and enhanced chemosensitivity and apoptosis to gefitinib in NSCLC cells. In this study, we describe the findings that overexpression of SphK2 promotes chemoresistance in NSCLC cells. Inhibition of SphK2 might be considered as a strategy in NSCLC treatment with gefitinib.
KeywordsLung cancer NSCLC SphK2 Gefitinib EGFR-TKI PC-9/GR cells Proliferation Apoptosis Chemoresistance
This work is supported by National Natural Science Foundation of China grant (No. 81172214, 81572276 to LC), National Natural Science Youth Foundation of China grant (No. 81501960 to JH), Health Department of Heilongjiang Province of China grant (No. 2013086 to JN), Harbin Medical University Cancer Hospital of China grant (No. JJMS2014-04 to JN, JJZ2011-02 to CL), and Harbin Bureau of Science and Technology grant (No. 2015RAQYJ101 to JN).
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