, Volume 130, Issue 2, pp 73-79
Date: 21 Nov 2003

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

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Abstract

Purpose

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) γ in three human colon cancer cell lines, HCT-15, DLD-1and LoVo.

Methods

Viable cell number was evaluated by the Alamar blue assay and apoptotic cell death by TUNEL methods. Expression of PPARγ 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.

Results

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 PPARγ mRNA and protein was demonstrated in DLD-1 and LoVo cells before TGZ treatment. After the treatment, PPARγ 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 PPARγ, villin or MUC2 mRNAs were not observed in DLD-1 cells.

Conclusions

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