title: [Role of SPHK1 regulates multi-drug resistance of small cell lung cancer  and its clinical significance].
abstract: OBJECTIVE
  Lung cancer is the leading cause of cancer-related deaths worldwide. Approximately 15% of all histological types consist of small cell lung cancer (SCLC). Chemotherapy is one of the major treatment method. Though the current first-line standard chemotherapy regimen for SCLC is active in most SCLC cases, however the disease recurs shortly after the first successful treatment with multi-drug resistance (MDR) phenotype. Our previously study showed that SPHK1 was associated with MDR in SCLC. The aim of this study is to investigate the role of sphingosine kinase 1 (SPHK1) showed in small cell lung multi-drug resistance.
  
  
  METHODS
  Firstly, the analysis of QRT-PCR and Western blot were used to study differential expression of SPHK1 from mRNA and protein levels in both the H69 and H69AR cell lines. Then, Downregulation of SPHK1 by transfection with siRNA in H69AR. Moreover, the sensitivities of cells to chemotherapy drugs such as ADM, DDP, VP-16 were detected by CCK8 assay. The change of cell cycle and apoptosis rate were detected by flow cytometry. Meanwhile, expression of SPHK1 in clinical specimens were detected by QT-PCR and immunohistochemistry. Relation of SPHK1 expression with clinicopathological features and prognosis of patients was studied.
  
  
  RESULTS
  The expression of SPHK1 was significantly decreased in H69AR cells that in the H69 cells. The sensitivities of H69AR cells to chemotherapy drugs were increased when up-regulated the expression of SPHK1, enforced SPHK1 expression increased cell apoptosis and the cell cycle arrest in G0/G1 phase in H69AR cells, the expression of SPHK1 was not associated with gender, age, but significantly correlated with clinical stage, chemosensitivity and overall survival (P<0.05).
  
  
  CONCLUSIONS
  Our results suggest that SPHK1 is involved in the regulation of small cell lung cancer multi-drug resistance, SPHK1 may be as potentialtarget gene to evaluate the chemosensitivity and clinical prognostic for SCLC.
authors.affiliation: Department of Oncology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610000, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Oncology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610000, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Oncology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610000, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Oncology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610000, China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Bai
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D016896:Treatment Outcome; D000099157:Sphingosine Kinase
chemical_list: D000970:Antineoplastic Agents; D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase