Peroxisome proliferator-activated receptor γ agonist efatutazone impairs transforming growth factor β2-induced motility of epidermal growth factor receptor tyrosine kinase inhibitor-resistant lung cancer cells.
Bottom Line: Efatutazone had no growth-inhibitory effect on the tested cells but inhibited the motility of EGFR-TKI-resistant cells in wound closure and transwell assays.Efatutazone plus erlotinib treatment provided greater inhibition of PC-9ER cell migration than efatutazone or erlotinib alone.These results suggest that efatutazone inhibits cell motility by antagonizing the TGF-β/Smad2 pathway and effectively prevents metastasis in NSCLC patients with acquired resistance to EGFR-TKI regardless of the resistance mechanism.
Affiliation: Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.Show MeSH
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Mentions: In this study, we demonstrated that the novel PPARγ agonist efatutazone attenuated the enhanced motility of EGFR-TKI-resistant NSCLC cells regardless of the resistance mechanism. This attenuation was mediated by inhibition of the TGF-β/Smad2 pathway via suppression of TGF-β2 mRNA expression (Fig. 5). These phenomena imply TGF-β2-mediated cross-talk between PPARγ and the TGF-β pathway. Several studies have been performed on the interaction between PPARγ and the TGF-β pathway.17,20–22
Affiliation: Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.