Abstract
Sphingosine kinase 1 (SphK1) is a tumor-associated protein overexpressed in numerous types of cancer and is involved in the regulation of resistance to multiple chemotherapeutic agents. However, the role of SphK1 in the resistance of hepatocellular carcinoma (HCC) to oxaliplatin remains unclear. In the present study, the transcriptional levels of SphK1 were analyzed in 21 patients with HCC and the SphK1 expression levels were identified to be significantly upregulated in HCC tissue compared with that in adjacent normal tissue samples (P<0.001). High SphK1 expression correlated with shorter overall survival times in patients with HCC (P<0.05). Furthermore, SphK1 expression levels and activity were analyzed in a series of HCC cell lines and they were both demonstrated to be associated with resistance to oxaliplatin. Conversely, the knockdown of SphK1 protein expression resulted in decreased oxaliplatin resistance in SK-Hep1 and HCCLM3 cell lines. In addition, the results of the current study demonstrated that the downregulation of SphK1 decreased the levels of phosphorylated AKT serine/threonine kinase (Akt) and glycogen synthase kinase-3β (GSK3β), suggesting that SphK1 promotes oxaliplatin resistance of HCC cells via modulation ...Continue Reading
References
Aug 18, 2005·Journal of Neuropathology and Experimental Neurology·James R Van BrocklynThomas W Prior
Mar 7, 2006·Nature Reviews. Drug Discovery·Gergely SzakácsMichael M Gottesman
Jan 24, 2007·Naunyn-Schmiedeberg's Archives of Pharmacology·Regina AlemanyDagmar Meyer Zu Heringdorf
Dec 7, 2007·Breast Cancer Research and Treatment·Eugen RuckhäberleManfred Kaufmann
Feb 1, 2008·Annals of Surgical Oncology·Melanie B ThomasPhilip Johnson
Feb 24, 2009·Annual Review of Biochemistry·Hugh RosenSteven Brown
Apr 18, 2009·Molecular Cancer Therapeutics·Julie Guillermet-GuibertCorinne Bousquet
Apr 23, 2009·Cancer Research·Isabelle AderOlivier Cuvillier
Aug 27, 2009·Endocrinology·Olga SukochevaPu Xia
Jun 18, 2010·Nature Reviews. Cancer·Nigel J Pyne, Susan Pyne
Jul 16, 2010·Nature Reviews. Gastroenterology & Hepatology·Ju Dong Yang, Lewis R Roberts
Oct 26, 2010·Progress in Lipid Research·Gauri A Patwardhan, Yong-Yu Liu
Nov 11, 2010·Future Oncology·Suriyan PonnusamyBesim Ogretmen
Feb 18, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Libing SongMengfeng Li
Feb 19, 2011·Current Oncology·T Alcindor, N Beauger
Mar 12, 2011·Experimental Hematology·Gabriella MarfeRaymond B Birge
Jul 16, 2011·Journal of Hepatology·Jing-Houng WangSheng-Nan Lu
Oct 6, 2011·Journal of Hepatology·Uzma Asghar, Tim Meyer
Oct 18, 2011·Trends in Cell Biology·Michael MaceykaSarah Spiegel
Nov 21, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Roberta RosaRoberto Bianco
Jan 8, 2013·Advances in Cancer Research·Linda A Heffernan-Stroud, Lina M Obeid
Aug 21, 2013·Nature Reviews. Drug Discovery·Gregory T KunkelSarah Spiegel
Feb 15, 2015·Biochemical and Biophysical Research Communications·Feng JiHaodong Fei
Citations
Jun 13, 2020·Pharmaceuticals·Sonam RoyMd Imtaiyaz Hassan
Jul 17, 2020·Frontiers in Oncology·Weiwei ShiChunping Jiang
May 1, 2021·Cancers·Preeti GuptaMd Imtaiyaz Hassan
Sep 24, 2019·Current Medicinal Chemistry·Petra GrbčićMirela Sedić