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Title: Combined therapeutic potential of nuclear receptors with receptor tyrosine kinase inhibitors in lung cancer

Highlights: • The 48 NR genes and 48 biological anti-cancer targets are profiled in paired-cells. • Growth inhibition by NR ligands or TKIs is target receptor level-dependent. • T0901317 with gefitinib/PHA665752 shows additive growth inhibition in lung cells. - Abstract: Cancer heterogeneity is a big hurdle in achieving complete cancer treatment, which has led to the emergence of combinational therapy. In this study, we investigated the potential use of nuclear receptor (NR) ligands for combinational therapy with other anti-cancer drugs. We first profiled all 48 NRs and 48 biological anti-cancer targets in four pairs of lung cell lines, where each pair was obtained from the same patient. Two sets of cell lines were normal and the corresponding tumor cell lines while the other two sets consisted of primary versus metastatic tumor cell lines. Analysis of the expression profile revealed 11 NRs and 15 cancer targets from the two pairs of normal versus tumor cell lines, and 9 NRs and 9 cancer targets from the primary versus metastatic tumor cell lines had distinct expression patterns in each category. Finally, the evaluation of nuclear receptor ligand T0901317 for liver X receptor (LXR) demonstrated its combined therapeutic potential with tyrosine kinase inhibitors. Themore » combined treatment of cMET inhibitor PHA665752 or EGFR inhibitor gefitinib with T0901317 showed additive growth inhibition in both H2073 and H1993 cells. Mechanistically, the combined treatment suppressed cell cycle progression by inhibiting cyclinD1 and cyclinB expression. Taken together, this study provides insight into the potential use of NR ligands in combined therapeutics with other biological anti-cancer drugs.« less
Authors:
 [1] ;  [2] ;  [2] ;  [3] ;  [1] ;  [2] ;  [2] ; ; ;  [1] ;  [3] ;  [4] ;  [1] ;  [2] ;  [2]
  1. Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of)
  2. (Korea, Republic of)
  3. Department of Pathology, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of)
  4. Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701 (Korea, Republic of)
Publication Date:
OSTI Identifier:
22416426
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 447; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL CYCLE; DRUGS; GENES; LIGANDS; LIVER; LUNGS; METASTASES; NEOPLASMS; PATIENTS; RECEPTORS; RESPIRATORY TRACT CELLS; THERAPY; TUMOR CELLS; TYROSINE