title: Effect of κ-opioid receptor agonist on the growth of non-small cell lung cancer (NSCLC) cells.
abstract: BACKGROUND
  It is becoming increasingly recognised that opioids are responsible for tumour growth. However, the effects of opioids on tumour growth have been controversial.
  
  
  METHODS
  The effects of κ-opioid receptor (KOR) agonist on the growth of non-small cell lung cancer (NSCLC) cells were assessed by a cell proliferation assay. Western blotting was performed to ascertain the mechanism by which treatment with KOR agonist suppresses tumour growth.
  
  
  RESULTS
  Addition of the selective KOR agonist U50,488H to gefitinib-sensitive (HCC827) and gefitinib-resistant (H1975) NSCLC cells produced a concentration-dependent decrease in their growth. These effects were abolished by co-treatment with the selective KOR antagonist nor-BNI. Furthermore, the growth-inhibitory effect of gefitinib in HCC827 cells was further enhanced by co-treatment with U50,488H. With regard to the inhibition of tumour growth, the addition of U50, 488H to H1975 cells produced a concentration-dependent decrease in phosphorylated-glycogen synthase kinase 3β (p-GSK3β).
  
  
  CONCLUSIONS
  The present results showed that stimulation of KOR reduces the growth of gefitinib-resistant NSCLC cells through the activation of GSK3β.
authors.affiliation: Department of Physiology, Keio University, School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kuzumaki
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Narita
authors.forename: T
authors.initials: T
authors.lastname: Hosoya
authors.forename: A
authors.initials: A
authors.lastname: Nagasawa
authors.forename: S
authors.initials: S
authors.lastname: Imai
authors.forename: K
authors.initials: K
authors.lastname: Yamamizu
authors.forename: H
authors.initials: H
authors.lastname: Morita
authors.forename: H
authors.initials: H
authors.lastname: Nagase
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: H J
authors.initials: HJ
authors.lastname: Okano
authors.forename: J K
authors.initials: JK
authors.lastname: Yamashita
authors.forename: H
authors.initials: H
authors.lastname: Okano
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Narita
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics; D000077156:Gefitinib; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D020125:Mutation, Missense; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D017473:Receptors, Opioid, kappa; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D066246:ErbB Receptors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D000077156:Gefitinib