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

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.