Inhibition of Heat-shock Protein 27 Reduces 5-Fluorouracil-acquired Resistance in Human Colon Cancer Cells.

BACKGROUND/AIM:In previous work we showed that expression of heat-shock protein 27 (HSP27; encoded by HSPB1) was associated with inherent resistance to 5-fluorouracil (5-FU). However, the relationship between HSP27 and acquired resistance remains unknown. MATERIALS AND METHODS:We generated an acquired resistance model (WiDr-R) of a colon cancer cell line by exposing WiDr cells to 5-FU. Cell viability assays under treatment with 5-FU, as well as down-regulation of HSP27 using small interfering HSP27 RNA, were performed. HSP27 mRNA and protein expression was analyzed using real-time polymerase chain reaction and western blotting. RESULTS:5-FU-acquired resistance induced overexpression of HSP27 mRNA and protein levels in WiDr-R cells. Furthermore, siRNA knockdown of HSP27 in WiDr-R cells reduced 5-FU-acquired resistance. CONCLUSION:These findings demonstrate that HSP27 is associated with 5-FU resistance in human colon cancer cell cells and suggest that HSP27 regulation represents a novel approach to overcoming chemoresistance in colorectal cancer.