title: Overexpression of Sphk2 is associated with gefitinib resistance in non-small cell lung cancer.
abstract: 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.
authors.affiliation: The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Haping Road 150, Harbin, 150040, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: The Thoracic Surgery Department, Harbin Medical University Cancer Hospital, Harbin, 150040, People's Republic of China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Ning
authors.affiliation: The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Haping Road 150, Harbin, 150040, People's Republic of China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Li
authors.affiliation: The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Haping Road 150, Harbin, 150040, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Haping Road 150, Harbin, 150040, People's Republic of China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Meng
authors.affiliation: The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Haping Road 150, Harbin, 150040, People's Republic of China.
authors.forename: Hailing
authors.initials: H
authors.lastname: Lu
authors.affiliation: The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Haping Road 150, Harbin, 150040, People's Republic of China. caili@ems.hrbmu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Cai
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D034741:RNA, Small Interfering / Q000235:genetics; D000099157:Sphingosine Kinase
chemical_list: D000077156:Gefitinib; D017853:Phosphotransferases (Alcohol Group Acceptor); D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D034741:RNA, Small Interfering; C000594250:sphingosine kinase 2, human; D000099157:Sphingosine Kinase
keywords: Apoptosis; Chemoresistance; EGFR-TKI; Gefitinib; Lung cancer; NSCLC; PC-9/GR cells; Proliferation; SphK2