Heat shock protein 27, a novel regulator of 5-fluorouracil resistance in colon cancer

Masashi Tsuruta, Hideki Nishibori, Hirotoshi Hasegawa, Yoshiyuki Ishii, Takashi Endo, Tetsuro Kubota, Masaki Kitajima, Yuukou Kitagawa

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The resistance of colon cancer to 5-fluorouracil (5-FU) is a critical issue, and the cause of this resistance cannot always be explained based on the known molecules. Heat shock protein 27 (HSP27) mRNA expression has recently been shown to be correlated with 5-FU resistance in 5-FU-resistant cell lines. In this study, we attempted to elucidate the functional mechanism of HSP27 in 5-FU resistance in colon cancer. HSP27 protein levels in several human colon cancer cell lines (LoVo, HCT15, WiDr, HCT116, HT-29 and SW480) were determined by immunoblot and densitometry analysis. The in vitro growth inhibition rates (IR) of the cell lines at various concentrations of 5-FU were assessed by MTT assay. The degree of 5-FU resistance was estimated as the drug concentration inducing 50% IR (IC50). The HSP27 protein level and IC50 were significantly correlated in these cell lines (p=0.010). The effect of HSP27 overexpression on IC50 was evaluated in LoVo cells. HSP27 transfectants significantly increased IC50 and reduced HSP27 resistance. The effect of HSP27 down-regulation by HSP27 siRNA on IC50 was confirmed in HCT15 cells. HSP27 siRNA suppressed HSP27 protein levels and reduced IC50 in a dose-dependent manner. These data indicated that HSP27 is closely connected with 5-FU resistance in colon cancer and suggested that HSP27 levels predicted 5-FU resistance. HSP27 down-regulation overcame 5-FU resistance and HSP27 may be a clinical target in patients with 5-FU-resistant colon cancer.

Original languageEnglish
Pages (from-to)1165-1172
Number of pages8
JournalOncology Reports
Volume20
Issue number5
DOIs
Publication statusPublished - 2008

Fingerprint

HSP27 Heat-Shock Proteins
Fluorouracil
Colonic Neoplasms
Cell Line
Small Interfering RNA
Down-Regulation
Proteins
Densitometry

Keywords

  • 5-fluorouracil
  • Colon cancer
  • Heat shock protein 27
  • RNA interference

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Heat shock protein 27, a novel regulator of 5-fluorouracil resistance in colon cancer. / Tsuruta, Masashi; Nishibori, Hideki; Hasegawa, Hirotoshi; Ishii, Yoshiyuki; Endo, Takashi; Kubota, Tetsuro; Kitajima, Masaki; Kitagawa, Yuukou.

In: Oncology Reports, Vol. 20, No. 5, 2008, p. 1165-1172.

Research output: Contribution to journalArticle

Tsuruta, M, Nishibori, H, Hasegawa, H, Ishii, Y, Endo, T, Kubota, T, Kitajima, M & Kitagawa, Y 2008, 'Heat shock protein 27, a novel regulator of 5-fluorouracil resistance in colon cancer', Oncology Reports, vol. 20, no. 5, pp. 1165-1172. https://doi.org/10.3892/or_00000125
Tsuruta, Masashi ; Nishibori, Hideki ; Hasegawa, Hirotoshi ; Ishii, Yoshiyuki ; Endo, Takashi ; Kubota, Tetsuro ; Kitajima, Masaki ; Kitagawa, Yuukou. / Heat shock protein 27, a novel regulator of 5-fluorouracil resistance in colon cancer. In: Oncology Reports. 2008 ; Vol. 20, No. 5. pp. 1165-1172.
@article{4435f85d2e804d2788e053be24acff18,
title = "Heat shock protein 27, a novel regulator of 5-fluorouracil resistance in colon cancer",
abstract = "The resistance of colon cancer to 5-fluorouracil (5-FU) is a critical issue, and the cause of this resistance cannot always be explained based on the known molecules. Heat shock protein 27 (HSP27) mRNA expression has recently been shown to be correlated with 5-FU resistance in 5-FU-resistant cell lines. In this study, we attempted to elucidate the functional mechanism of HSP27 in 5-FU resistance in colon cancer. HSP27 protein levels in several human colon cancer cell lines (LoVo, HCT15, WiDr, HCT116, HT-29 and SW480) were determined by immunoblot and densitometry analysis. The in vitro growth inhibition rates (IR) of the cell lines at various concentrations of 5-FU were assessed by MTT assay. The degree of 5-FU resistance was estimated as the drug concentration inducing 50{\%} IR (IC50). The HSP27 protein level and IC50 were significantly correlated in these cell lines (p=0.010). The effect of HSP27 overexpression on IC50 was evaluated in LoVo cells. HSP27 transfectants significantly increased IC50 and reduced HSP27 resistance. The effect of HSP27 down-regulation by HSP27 siRNA on IC50 was confirmed in HCT15 cells. HSP27 siRNA suppressed HSP27 protein levels and reduced IC50 in a dose-dependent manner. These data indicated that HSP27 is closely connected with 5-FU resistance in colon cancer and suggested that HSP27 levels predicted 5-FU resistance. HSP27 down-regulation overcame 5-FU resistance and HSP27 may be a clinical target in patients with 5-FU-resistant colon cancer.",
keywords = "5-fluorouracil, Colon cancer, Heat shock protein 27, RNA interference",
author = "Masashi Tsuruta and Hideki Nishibori and Hirotoshi Hasegawa and Yoshiyuki Ishii and Takashi Endo and Tetsuro Kubota and Masaki Kitajima and Yuukou Kitagawa",
year = "2008",
doi = "10.3892/or_00000125",
language = "English",
volume = "20",
pages = "1165--1172",
journal = "Oncology Reports",
issn = "1021-335X",
publisher = "Spandidos Publications",
number = "5",

}

TY - JOUR

T1 - Heat shock protein 27, a novel regulator of 5-fluorouracil resistance in colon cancer

AU - Tsuruta, Masashi

AU - Nishibori, Hideki

AU - Hasegawa, Hirotoshi

AU - Ishii, Yoshiyuki

AU - Endo, Takashi

AU - Kubota, Tetsuro

AU - Kitajima, Masaki

AU - Kitagawa, Yuukou

PY - 2008

Y1 - 2008

N2 - The resistance of colon cancer to 5-fluorouracil (5-FU) is a critical issue, and the cause of this resistance cannot always be explained based on the known molecules. Heat shock protein 27 (HSP27) mRNA expression has recently been shown to be correlated with 5-FU resistance in 5-FU-resistant cell lines. In this study, we attempted to elucidate the functional mechanism of HSP27 in 5-FU resistance in colon cancer. HSP27 protein levels in several human colon cancer cell lines (LoVo, HCT15, WiDr, HCT116, HT-29 and SW480) were determined by immunoblot and densitometry analysis. The in vitro growth inhibition rates (IR) of the cell lines at various concentrations of 5-FU were assessed by MTT assay. The degree of 5-FU resistance was estimated as the drug concentration inducing 50% IR (IC50). The HSP27 protein level and IC50 were significantly correlated in these cell lines (p=0.010). The effect of HSP27 overexpression on IC50 was evaluated in LoVo cells. HSP27 transfectants significantly increased IC50 and reduced HSP27 resistance. The effect of HSP27 down-regulation by HSP27 siRNA on IC50 was confirmed in HCT15 cells. HSP27 siRNA suppressed HSP27 protein levels and reduced IC50 in a dose-dependent manner. These data indicated that HSP27 is closely connected with 5-FU resistance in colon cancer and suggested that HSP27 levels predicted 5-FU resistance. HSP27 down-regulation overcame 5-FU resistance and HSP27 may be a clinical target in patients with 5-FU-resistant colon cancer.

AB - The resistance of colon cancer to 5-fluorouracil (5-FU) is a critical issue, and the cause of this resistance cannot always be explained based on the known molecules. Heat shock protein 27 (HSP27) mRNA expression has recently been shown to be correlated with 5-FU resistance in 5-FU-resistant cell lines. In this study, we attempted to elucidate the functional mechanism of HSP27 in 5-FU resistance in colon cancer. HSP27 protein levels in several human colon cancer cell lines (LoVo, HCT15, WiDr, HCT116, HT-29 and SW480) were determined by immunoblot and densitometry analysis. The in vitro growth inhibition rates (IR) of the cell lines at various concentrations of 5-FU were assessed by MTT assay. The degree of 5-FU resistance was estimated as the drug concentration inducing 50% IR (IC50). The HSP27 protein level and IC50 were significantly correlated in these cell lines (p=0.010). The effect of HSP27 overexpression on IC50 was evaluated in LoVo cells. HSP27 transfectants significantly increased IC50 and reduced HSP27 resistance. The effect of HSP27 down-regulation by HSP27 siRNA on IC50 was confirmed in HCT15 cells. HSP27 siRNA suppressed HSP27 protein levels and reduced IC50 in a dose-dependent manner. These data indicated that HSP27 is closely connected with 5-FU resistance in colon cancer and suggested that HSP27 levels predicted 5-FU resistance. HSP27 down-regulation overcame 5-FU resistance and HSP27 may be a clinical target in patients with 5-FU-resistant colon cancer.

KW - 5-fluorouracil

KW - Colon cancer

KW - Heat shock protein 27

KW - RNA interference

UR - http://www.scopus.com/inward/record.url?scp=58149327400&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149327400&partnerID=8YFLogxK

U2 - 10.3892/or_00000125

DO - 10.3892/or_00000125

M3 - Article

C2 - 18949417

AN - SCOPUS:58149327400

VL - 20

SP - 1165

EP - 1172

JO - Oncology Reports

JF - Oncology Reports

SN - 1021-335X

IS - 5

ER -