Limits...
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.

Show MeSH

Related in: MedlinePlus

Efatutazone treatment significantly suppresses the mRNA expression and secretion of transforming growth factor β2 (TGF-β2). (a) mRNA levels of TGF-β1 and TGF-β2 after incubation for 12 h in FBS-free medium with DMSO (0.1%; control) or efatutazone (10 μmol/L) were measured by qRT-PCR. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's t-test). The error bars indicate the standard deviations of the mean. (b) Cells were seeded and incubated in six-well plates for 60 h in FBS-free medium with DMSO (0.1%; control) or efatutazone (10 μmol/L). Conditioned medium was collected, and TGF-β1 and TGF-β2 levels were measured by ELISA. **P < 0.01; ***P < 0.001 (Student's t-test). The error bars indicate the standard deviations of the mean. The amount of TGF-β2 in PC-9 cells treated with efatutazone was below the detection limit. ND, not detected.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4317891&req=5

fig02: Efatutazone treatment significantly suppresses the mRNA expression and secretion of transforming growth factor β2 (TGF-β2). (a) mRNA levels of TGF-β1 and TGF-β2 after incubation for 12 h in FBS-free medium with DMSO (0.1%; control) or efatutazone (10 μmol/L) were measured by qRT-PCR. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's t-test). The error bars indicate the standard deviations of the mean. (b) Cells were seeded and incubated in six-well plates for 60 h in FBS-free medium with DMSO (0.1%; control) or efatutazone (10 μmol/L). Conditioned medium was collected, and TGF-β1 and TGF-β2 levels were measured by ELISA. **P < 0.01; ***P < 0.001 (Student's t-test). The error bars indicate the standard deviations of the mean. The amount of TGF-β2 in PC-9 cells treated with efatutazone was below the detection limit. ND, not detected.

Mentions: We previously reported that PC-9ER cells acquire enhanced motility via TGF-β2-induced activation of the TGF-β/Smad2 pathway, which plays an important role in cell motility and migration.15,19 Therefore, we evaluated the effect of efatutazone on the transcription and secretion of TGF-β ligands. The basal mRNA levels of TGF-β2 in PC-9ER and PC-9ZD cells were higher than those in PC-9 cells. In contrast, no significant differences in the mRNA levels of TGF-β1 were observed among these cell lines (Fig. 2a). Efatutazone treatment suppressed TGF-β2 mRNA expression in all cells, whereas it did not suppress TGF-β1 mRNA expression (Fig. 2a). PC-9ER and PC-9ZD cells secreted significantly higher amounts of TGF-β2 than PC-9 cells did; however, PC-9ER and PC-9ZD cells did not secrete higher levels of TGF-β1 (Fig. 2b). Efatutazone significantly inhibited the secretion of TGF-β2 from all cells, confirming the effect of efatutazone on TGF-β2 transcription (Fig. 2b). These results indicate that efatutazone treatment significantly suppresses TGF-β2 secretion, by suppressing TGF-β2 mRNA expression.


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)

Efatutazone treatment significantly suppresses the mRNA expression and secretion of transforming growth factor β2 (TGF-β2). (a) mRNA levels of TGF-β1 and TGF-β2 after incubation for 12 h in FBS-free medium with DMSO (0.1%; control) or efatutazone (10 μmol/L) were measured by qRT-PCR. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's t-test). The error bars indicate the standard deviations of the mean. (b) Cells were seeded and incubated in six-well plates for 60 h in FBS-free medium with DMSO (0.1%; control) or efatutazone (10 μmol/L). Conditioned medium was collected, and TGF-β1 and TGF-β2 levels were measured by ELISA. **P < 0.01; ***P < 0.001 (Student's t-test). The error bars indicate the standard deviations of the mean. The amount of TGF-β2 in PC-9 cells treated with efatutazone was below the detection limit. ND, not detected.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: Efatutazone treatment significantly suppresses the mRNA expression and secretion of transforming growth factor β2 (TGF-β2). (a) mRNA levels of TGF-β1 and TGF-β2 after incubation for 12 h in FBS-free medium with DMSO (0.1%; control) or efatutazone (10 μmol/L) were measured by qRT-PCR. *P < 0.05; **P < 0.01; ***P < 0.001 (Student's t-test). The error bars indicate the standard deviations of the mean. (b) Cells were seeded and incubated in six-well plates for 60 h in FBS-free medium with DMSO (0.1%; control) or efatutazone (10 μmol/L). Conditioned medium was collected, and TGF-β1 and TGF-β2 levels were measured by ELISA. **P < 0.01; ***P < 0.001 (Student's t-test). The error bars indicate the standard deviations of the mean. The amount of TGF-β2 in PC-9 cells treated with efatutazone was below the detection limit. ND, not detected.
Mentions: We previously reported that PC-9ER cells acquire enhanced motility via TGF-β2-induced activation of the TGF-β/Smad2 pathway, which plays an important role in cell motility and migration.15,19 Therefore, we evaluated the effect of efatutazone on the transcription and secretion of TGF-β ligands. The basal mRNA levels of TGF-β2 in PC-9ER and PC-9ZD cells were higher than those in PC-9 cells. In contrast, no significant differences in the mRNA levels of TGF-β1 were observed among these cell lines (Fig. 2a). Efatutazone treatment suppressed TGF-β2 mRNA expression in all cells, whereas it did not suppress TGF-β1 mRNA expression (Fig. 2a). PC-9ER and PC-9ZD cells secreted significantly higher amounts of TGF-β2 than PC-9 cells did; however, PC-9ER and PC-9ZD cells did not secrete higher levels of TGF-β1 (Fig. 2b). Efatutazone significantly inhibited the secretion of TGF-β2 from all cells, confirming the effect of efatutazone on TGF-β2 transcription (Fig. 2b). These results indicate that efatutazone treatment significantly suppresses TGF-β2 secretion, by suppressing TGF-β2 mRNA expression.

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