Sprouty2 (Spry2) was identified recently as a tumor suppressor gene in cancer 
cells which inhibits the activation of receptor tyrosine kinases (RTKs). The 
present study explored the effect of Spry2 in colon cancer cells in order to 
assess its potential use in the treatment of colon cancer. Expression of Spry2 
inhibited the growth of a colon cancer cell line, HCT116, and induced 
sensitization to fluorouracil (5-FU) and metformin. Spry2 promoted apoptosis of 
cancer cells in association with activation of the phosphatase and tensin 
homolog deleted on chromosome 10 (PTEN) pathway and the blockade of Ras-Raf-Erk 
signaling. Treatment of Spry2-HCT116 cells with metformin resulted in a more 
prominent effect on the inhibition of cell migration. Inhibition of microRNA-21 
(mir‑21) induced upregulation of Spry2 and PTEN which underscores the importance 
of mir-21 in Spry2-associated tumorigenesis of the colon. These results point 
toward a potential strategy for colon cancer treatment worthy of further 
investigation.