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Cyclin E overexpression confers resistance to the CDK4/6 specific inhibitor palbociclib in gastric cancer cells

Cited 28 time in Web of Science Cited 28 time in Scopus
Issue Date
2018-05
Citation
Cancer Letters, Vol.430, pp.123-132
Keywords
PalbociclibGastric cancerCyclin ECell cycle5-FU
Abstract
Palbociclib is a specific inhibitor of CDK4/6 and has been shown to provide a survival benefit in hormone receptor-positive advanced breast cancer. TCGA database reported that about half of gastric cancers exhibit abnormalities in cell-cycle-related molecules, suggesting that gastric cancer is a good candidate for palbociclib treatment; however, the antitumor effects and predictive markers of palbociclib in gastric cancer remain incompletely described. Herein, the effect and predictive markers of palbociclib on gastric cancer cells were investigated. Our results reveal that palbociclib showed anti-proliferative effects by inducing G1 phase cell-cycle arrest and cellular senescence in some gastric cancer cells. Basal protein expression level of cyclin E showed an inverse correlation of cancer cell sensitivity to palbociclib. In addition, palbociclib enhanced the antitumor effect of 5-FU in vitro and in vivo by modulating thymidine synthase expression. These results suggest that cyclin E protein expression determines the anti proliferative effect of palbociclib, and palbociclib acts synergistically with 5-FU in gastric cancer. These findings provide a rationale for future clinical trials of palbociclib and 5-FU combination-based chemotherapy in gastric cancer. (C) 2018 Published by Elsevier B.V.
ISSN
0304-3835
URI
https://hdl.handle.net/10371/173176
DOI
https://doi.org/10.1016/j.canlet.2018.04.037
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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