4.3 Article

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

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ANTICANCER RESEARCH
卷 41, 期 3, 页码 1283-1290

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INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.14885

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Heat-shock protein 27; colorectal cancer; chemotherapy; 5-fluorouracil resistance

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The study shows that HSP27 is associated with 5-FU resistance in human colon cancer cells, and knocking down HSP27 using siRNA can reduce 5-FU acquired resistance. This suggests that HSP27 regulation could be a novel approach for overcoming chemoresistance in colorectal cancer.
Background/Aim: In previous work we showed that expression of heat-shock protein 27 (HSP27; encoded by HSPB1) was associated with inherent resistance to 5fluorouracil (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.

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