Role of SPHK1 Regulates Multi-drug Resistance of Small Cell Lung Cancer and Its Clinical Signiifcance
10.3779/j.issn.1009-3419.2014.11.01
- VernacularTitle:SPHK1在调节小细胞肺癌多药耐药中的作用
- Author:
YANG LAN
1
;
HU HONGLIN
;
DENG YING
;
BAI YIFENG
Author Information
1. 四川省人民医院肿瘤科
- Keywords:
Sphingosine kinase 1 (SPHK1);
Multi-drug resistance;
Lung neoplasms
- From:
Chinese Journal of Lung Cancer
2014;(11):769-777
- CountryChina
- Language:Chinese
-
Abstract:
Background and objective Lung cancer is the leading cause of cancer-related deaths worldwide. Ap-proximately 15%of all histological types consist of small cell lung cancer (SCLC). Chemotherapy is one of the major treatment method. hTough the current ifrst-line standard chemotherapy regimen for SCLC is active in most SCLC cases, however the disease recurs shortly atfer the ifrst successful treatment with multi-drug resistance (MDR) phenotype. Our previously study showed that SPHK1 was associated with MDR in SCLC. hTe 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. hTen, 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. hTe change of cell cycle and apoptosis rate were detected by lfow cytometry. Meanwhile, expression of SPHK1 in clinical specimens were detected by QT-PCR and immunohistochemistry. Re-lation of SPHK1 expression with clinicopathological features and prognosis of patients was studied. Results hTe expression of SPHK1 was signiifcantly decreased in H69AR cells that in the H69 cells. hTe 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 signiif-cantly correlated with clinical stage, chemosensitivity and overall survival (P<0.05). Conclusion 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.
