ROSIGLITAZONE: A POTENTIAL NEW STROMA TARGETED THERAPEUTIC AGENT IN COLON CANCER

Introduction The impact of tumour associated stroma on cancer cell invasion and metastasis is an attractive emerging field. Using Nanostring Pancancer pathway we have previously identified pro-fibrotic genes collagen type 1, alpha 1 (COL1A1), fibroblast growth factor 7 (FGF7) and secreted frizzled related protein 2 (SFRP2) significantly up regulated in human colon cancer peritumour adipose tissue compared to distal adipose tissue. Aim of this study was to evaluate the effect of Rosiglitazone, a peroxisome proliferator-activated receptor gamma (PPARG) agonist known to have anti fibrogenic properties, on COL1A1, FGF7 and SFRP2. Methods The effect of Rosiglitazone on COL1A1 and SFRP2 was evaluated employing in vitro co-culture systems. 3T3 L1 murine adipocytes were co-cultured with HCT 116 colon cancer cells with and without 1 nM Rosiglitazone for 72 hours. COL1A1, FGF7 and SFRP2 expression were evaluated using quantitative real time-polymerase chain reaction (qRT-PCR). Statistical analysis was performed using paired Student’s t-test with a cut-off of p-value Results Both COL1A1 and SFRP2 resulted significantly downregulated in co-cultured 3T3 L1 adipocytes treated with Rosiglitazone compared to untreated co-cultured 3T3 L1 adipocytes (20 fold change, p=0.02; 3.3 fold change, p=0.01 respectively). We did not observe any significant effect of Rosiglitazone on FGF7 expression in treated 3T3 L1 adipocytes compared to untreated adipocytes. Conclusion Our results have demonstrated significant down regulation of pro-fibrotic genes COL1A1 and SFRP2 in mature adipocytes induced by Rosiglitazone. Rosiglitazone may represent a novel therapeutic agent in stromal targeted therapy in colon cancer.