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J Cancer Res Clin Oncol. 2004 Feb;130(2):73-9. Epub 2003 Nov 21.

Induction of differentiation and peroxisome proliferator-activated receptor gamma expression in colon cancer cell lines by troglitazone.

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Second Department of Pathology, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8562, Japan.



We investigated the relationship between the effects of troglitazone (TGZ) on cellular growth, differentiation and apoptosis induction, and the induction of peroxisome proliferator-activated receptor (PPAR) gamma in three human colon cancer cell lines, HCT-15, DLD-1and LoVo.


Viable cell number was evaluated by the Alamar blue assay and apoptotic cell death by TUNEL methods. Expression of PPARgamma mRNA and protein was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The differentiation markers of colonic mucosa, villin and MUC2 mRNAs, were analyzed by real-time RT-PCR.


HCT-15 and DLD-1 cells proliferated rapidly while LoVo cells grew slowly. TGZ dose-dependently inhibited the proliferation of all the cell lines, and also induced apoptotic cell death. High expression of PPARgamma mRNA and protein was demonstrated in DLD-1 and LoVo cells before TGZ treatment. After the treatment, PPARgamma mRNA and protein levels were increased in HCT-15 and LoVo cells. Villin and MUC2 mRNAs were increased by TGZ treatment in HCT-15 cells while villin mRNA was repressed in LoVo cells. Changes in expression of PPARgamma, villin or MUC2 mRNAs were not observed in DLD-1 cells.


These results suggest that PPARgamma levels are not correlated with the rates of cell proliferation. Differentiation induction by TGZ was only observed in the cell lines with enhanced PPARgamma expression.

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