Combined therapeutic potential of nuclear receptors with receptor tyrosine kinase inhibitors in lung cancer |
| |
Authors: | Peninah M Wairagu Kwang Hwa Park Jihye Kim Jong-Whan Choi Hyun-Won Kim Byung-Il Yeh Soon-Hee Jung Suk-Joong Yong Yangsik Jeong |
| |
Institution: | 1. Department of Biochemistry, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701, Republic of Korea;2. Institute of Lifestyle Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701, Republic of Korea;3. Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701, Republic of Korea;4. Department of Pathology, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701, Republic of Korea;5. Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do 220-701, Republic of Korea |
| |
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. The 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. |
| |
Keywords: | Combinational therapy PPARγ LXR Lung cancer Tyrosine kinase inhibitors |
本文献已被 ScienceDirect 等数据库收录! |
|