[The impact of decreased Stat3 activation on 5-fluorouracil resistance of human gastric cancer cell line].
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.
Yu
Li-fen
LF
Department of Gastroenterology, Ruijin Hospital of Shanghai Second Medical University, Shanghai, 200025 China.
Chen
Ying
Y
Qiao
Min-min
MM
Zhang
Yong-ping
YP
Wu
Yun-lin
YL
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D005472:Fluorouracil