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


Journal

Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988

Informations de publication

Date de publication:
Mar 2021
Historique:
received: 30 12 2020
revised: 13 02 2021
accepted: 15 02 2021
entrez: 31 3 2021
pubmed: 1 4 2021
medline: 13 4 2021
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND/AIM OBJECTIVE
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 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 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 CONCLUSIONS
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.

Identifiants

pubmed: 33788719
pii: 41/3/1283
doi: 10.21873/anticanres.14885
doi:

Substances chimiques

HSP27 Heat-Shock Proteins 0
Fluorouracil U3P01618RT

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1283-1290

Informations de copyright

Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Auteurs

Yusuke Asada (Y)

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Masashi Tsuruta (M)

Department of Surgery, Keio University School of Medicine, Tokyo, Japan; masashitsuruta@gmail.com.
Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare School of Medicine, Narita, Japan.

Koji Okabayashi (K)

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Kohei Shigeta (K)

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Takashi Ishida (T)

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare School of Medicine, Narita, Japan.

Takehiro Shimada (T)

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Hirofumi Suzumura (H)

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Kaoru Koishikawa (K)

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Shingo Akimoto (S)

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

Hirotoshi Hasegawa (H)

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Department of Surgery, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Japan.

Yuko Kitagawa (Y)

Department of Surgery, Keio University School of Medicine, Tokyo, Japan.

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Classifications MeSH