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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.

Serizawa M, Murakami H, Watanabe M, Takahashi T, Yamamoto N, Koh Y - Cancer Sci. (2014)

Bottom Line: Efatutazone, a novel peroxisome proliferator-activated receptor gamma (PPARγ) agonist, is currently under clinical evaluation; it has antiproliferative effects and induces cellular morphological changes and differentiation.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.

View Article: PubMed Central - PubMed

Affiliation: Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.

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Related in: MedlinePlus

Proposed mechanisms underlying the effect of efatutazone in erlotinib-resistant non-small cell lung cancers (NSCLC) cells. (a) The enhanced motility of PC-9ER and PC-9ZD cells was induced by activation of the transforming growth factor β (TGF-β) pathway due to increased TGF-β2 mRNA expression and subsequent secretion. (b) Enhanced motility of PC-9ER and PC-9ZD cells was suppressed by treatment with efatutazone. Efatutazone treatment significantly antagonized TGF-β2-mediated activation of the TGF-β pathway by suppressing TGF-β2 mRNA expression. The effect of efatutazone on TGF-β2 expression may not be due to direct activation of peroxisome proliferator-activated receptor gamma (PPARγ) signaling. The mechanism underlying efatutazone-mediated TGF-β2 downregulation requires further study.
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fig05: Proposed mechanisms underlying the effect of efatutazone in erlotinib-resistant non-small cell lung cancers (NSCLC) cells. (a) The enhanced motility of PC-9ER and PC-9ZD cells was induced by activation of the transforming growth factor β (TGF-β) pathway due to increased TGF-β2 mRNA expression and subsequent secretion. (b) Enhanced motility of PC-9ER and PC-9ZD cells was suppressed by treatment with efatutazone. Efatutazone treatment significantly antagonized TGF-β2-mediated activation of the TGF-β pathway by suppressing TGF-β2 mRNA expression. The effect of efatutazone on TGF-β2 expression may not be due to direct activation of peroxisome proliferator-activated receptor gamma (PPARγ) signaling. The mechanism underlying efatutazone-mediated TGF-β2 downregulation requires further study.

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


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.

Serizawa M, Murakami H, Watanabe M, Takahashi T, Yamamoto N, Koh Y - Cancer Sci. (2014)

Proposed mechanisms underlying the effect of efatutazone in erlotinib-resistant non-small cell lung cancers (NSCLC) cells. (a) The enhanced motility of PC-9ER and PC-9ZD cells was induced by activation of the transforming growth factor β (TGF-β) pathway due to increased TGF-β2 mRNA expression and subsequent secretion. (b) Enhanced motility of PC-9ER and PC-9ZD cells was suppressed by treatment with efatutazone. Efatutazone treatment significantly antagonized TGF-β2-mediated activation of the TGF-β pathway by suppressing TGF-β2 mRNA expression. The effect of efatutazone on TGF-β2 expression may not be due to direct activation of peroxisome proliferator-activated receptor gamma (PPARγ) signaling. The mechanism underlying efatutazone-mediated TGF-β2 downregulation requires further study.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317891&req=5

fig05: Proposed mechanisms underlying the effect of efatutazone in erlotinib-resistant non-small cell lung cancers (NSCLC) cells. (a) The enhanced motility of PC-9ER and PC-9ZD cells was induced by activation of the transforming growth factor β (TGF-β) pathway due to increased TGF-β2 mRNA expression and subsequent secretion. (b) Enhanced motility of PC-9ER and PC-9ZD cells was suppressed by treatment with efatutazone. Efatutazone treatment significantly antagonized TGF-β2-mediated activation of the TGF-β pathway by suppressing TGF-β2 mRNA expression. The effect of efatutazone on TGF-β2 expression may not be due to direct activation of peroxisome proliferator-activated receptor gamma (PPARγ) signaling. The mechanism underlying efatutazone-mediated TGF-β2 downregulation requires further study.
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

Bottom Line: Efatutazone, a novel peroxisome proliferator-activated receptor gamma (PPARγ) agonist, is currently under clinical evaluation; it has antiproliferative effects and induces cellular morphological changes and differentiation.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.

View Article: PubMed Central - PubMed

Affiliation: Drug Discovery and Development Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.

Show MeSH
Related in: MedlinePlus