Abstract
This study evaluated the preclinical activity of selumetinib (AZD6244, ARRY-142866), an inhibitor of the mitogen-activated protein kinase kinase (MAPKK or MEK1/2) in 6 nasopharyngeal cancer (NPC) cell lines. Selumetinib could achieve up to 90 % inhibition of cell growth with the respective IC(50) values in NPC cell lines as follow: HK1 = 0.04 μM, HK1-LMP1(B95.8) = 0.17 μM, HONE-1-EBV = 0.46 μM, HONE-1 = 1.79 μM, CNE-2 = 2.20 μM and C666-1 > 10 μM. The drug-sensitive cell lines HK1, HK1-LMP1(B95.8) and HONE-1-EBV have higher basal expression of phosphorylated (pi)-MAPK than the less sensitive cell lines. BRAF mutations were not detected in all 6 cell lines. Re-introduction of the EBV genome into HONE-1 cells, generating the HONE-1-EBV cell line, seemed to result in elevated expression of pi-MAPK and sensitivity to selumetinib when compared with the parental HONE-1 cells. At a concentration of 0.5 μM and 5 μM, selumetinib induced apoptosis (as indicated by cleaved PARP expression and caspase 3 induction), and G(0)/G(1) cycle arrest in HONE-1-EBV and HK1-LMP1(B95.8) cells. The combination of selumetinib (at IC(25) concentration) and the EGFR tyrosine kinase inhibitor, gefitinib (at concentrations of 0.1, 3 and 9 μM) resulted in sy...Continue Reading
References
Feb 4, 1998·Virology·M L Roberts, N R Cooper
Feb 12, 2002·International Journal of Oncology·Angela Bik-Yu HuiDolly P Huang
Nov 27, 2002·Seminars in Cancer Biology·Sai Wah TsaoDolly P Huang
May 15, 2003·Laboratory Investigation; a Journal of Technical Methods and Pathology·Angela Kwok Fung LoGeorge Sai Wah Tsao
Aug 23, 2005·International Journal of Cancer. Journal International Du Cancer·Yvonne Yan-Yan OrKwok-Wai Lo
Sep 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Muralidhar BeeramEric K Rowinsky
Nov 8, 2005·Nature·David B SolitNeal Rosen
Apr 14, 2006·Neoplasia : an International Journal for Oncology Research·Angela Kwok Fung LoDolly P Huang
Sep 14, 2006·Pharmacological Reviews·Ting-Chao Chou
Nov 28, 2006·Cancer Letters·Anamaria Brozovic, Maja Osmak
Mar 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tammie C YehEli Wallace
Jul 13, 2007·Journal of Virology·Bernardo A MainouNancy Raab-Traub
Aug 19, 2007·Molecular Cancer Therapeutics·Barry R DaviesPaul D Smith
Sep 1, 2007·Cancer Chemotherapy and Pharmacology·Brigette MaAnthony T C Chan
Sep 19, 2007·Molecular Cancer Therapeutics·Hung HuynhKhee-Chee Soo
Dec 20, 2007·Cancer Research·Juan WangGen Sheng Wu
Jan 4, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nikolas K HaassKeiran S M Smalley
Jan 18, 2008·Journal of Virology·Christopher W DawsonLawrence S Young
Aug 5, 2008·Cancer Research·Bret B FridayAlex A Adjei
Aug 30, 2008·The Journal of Clinical Investigation·Arkaitz CarracedoPier Paolo Pandolfi
Nov 18, 2008·Medical Oncology·Chu-Chung ChouChin-Yuan Tzen
Jul 29, 2009·International Journal of Cancer. Journal International Du Cancer·Kathryn BalmannoSimon J Cook
Sep 17, 2009·Molecular Cancer Therapeutics·Young-Kwang YoonTae-You Kim
Sep 17, 2009·Investigational New Drugs·Brigette B Y MaSuk Hang Cheng
Aug 12, 2010·Cancer Research·Ensar HalilovicNeal Rosen
Dec 2, 2010·Cancer Research·Juyong YoonKang-Yell Choi
Dec 7, 2010·Biochemical and Biophysical Research Communications·Hyunho YoonHyo Jeong Hong
Mar 30, 2011·Cancer Research·Bingbing DaiJack A Roth
May 24, 2011·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Qiang ZuoWangjun Liao
Citations
Nov 13, 2012·Investigational New Drugs·Brigette B Y MaAnthony T C Chan
Jan 1, 2014·Cell Biology International·Xiao-Bin LvXiuju Wang
Apr 8, 2016·Expert Opinion on Investigational Drugs·Paolo Bossi, Salvatore Alfieri
Oct 31, 2014·Journal of Virology·Pok Man HauSai Wah Tsao
Sep 29, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ying Cheng, Hongqi Tian
Apr 21, 2017·Investigational New Drugs·Jeffrey R InfantePatricia M LoRusso