[The impact of decreased Stat3 activation on 5-fluorouracil resistance of human gastric cancer cell line]

Zhonghua Nei Ke Za Zhi. 2004 Dec;43(12):903-6.
[Article in Chinese]

Abstract

Objective: To investigate the relationship between different activation of Stat3 signaling and the drug resistance mechanisms in two human gastric cancer cell lines, 5-fluorouracil (5-FU) resistant cell line and its parental cell line.

Methods: Electrophoretic mobility shift assay and Western blot were used to detected Stat3 DNA-binding activity and the expression of phospho-Stat3 protein in 5-FU resistant cell line SGC7901/R and its parental cell line SGC7901, respectively. The mRNA expression of Stat3 and vascular endothelial growth factor (VEGF) were analysed with semi-quantitative RT-PCR. The expressive intensity of VEGF protein was measured by immunocytochemistry.

Results: The constitutive activation of Stat3 and the expression of phospho-Stat3 protein were different in two human gastric cancer cell lines. Compared with the parental cell line SGC7901, the Stat3-DNA binding activity and the expressive intensity of phospho-Stat3 protein were lower in the drug-resistant cell line SGC7901/R. The expression level of Stat3 mRNA was also decreased in drug resistant cell line, so did VEGF mRNA and its encoded protein.

Conclusions: The decreased Stat3 activation in 5-FU resistant human gastric cancer cell line SGC7901/R is related to the drug resistance mechanisms and may be correlated with the lower VEGF expression.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drug Resistance, Neoplasm
  • Fluorouracil / pharmacology*
  • Humans
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Phosphorylation
  • RNA, Messenger / genetics
  • STAT3 Transcription Factor
  • Signal Transduction / physiology
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antimetabolites, Antineoplastic
  • DNA-Binding Proteins
  • NF-kappa B
  • RNA, Messenger
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Vascular Endothelial Growth Factor A
  • Fluorouracil