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Synergistic induction of ICAM-1 expression by cisplatin and 5-fluorouracil in a cancer cell line via a NF-κB independent pathway.

Synergistic induction of ICAM-1 expression by cisplatin and 5-fluorouracil in a cancer cell line via a NF-κB independent pathway.

Authors :
Takizawa, K
Kamijo, R
Ito, D
Hatori, M
Sumitani, K
Nagumo, M
Source :
British Journal of Cancer. 6/1/99, Vol. 80 Issue 7, p954. 10p.
Publication Year :
1999

Abstract

Cisplatin (CDDP) and 5-fluorouracil (5-FU) are common anti-tumour agents, and the anti-tumour effect of CDDP and 5-FU are synergistically enhanced by combined treatment. To clarify the mechanisms of this synergism, we examined the effect of CDDP and 5-FU on the expression of cell adhesion molecules involved in recognition of cancer cells by T lymphocytes. When NA cells, a squamous cell carcinoma cell line, were exposed to CDDP and 5-FU for 18 h, the expression of intercellular adhesion molecule-1 (ICAM-1) was synergistically induced, whereas CDDP or 5-FU alone did not induce the expression of ICAM-1, as determined by flow cytometry. Expression of ICAM-2 and ICAM-3, which are recognized by the same counter receptor on T-cells, were not up-regulated by CDDP and 5-FU. RT-PCR analysis showed that the induction of ICAM-1 on NA cells might be due to transcriptional induction of ICAM-1 mRNA. Treatment with genistein, a protein tyrosine kinase (PTK) inhibitor, inhibited the induction of ICAM-1 on NA cells by CDDP and 5-FU, whereas staurosporin, a protein kinase C inhibitor, did not. Although CDDP and 5-FU induced binding at the nuclear factor kappa B (NF-κB) site in the ICAM-1 promoter, pretreatment with genistein did not prevent CDDP and 5-FU-induced binding at the NF-κB site. Moreover, a NF-κB nuclear translocation inhibitor did not inhibit the induction of ICAM-1 expression by treatment with CDDP and 5-FU. The synergistic effect of CDDP and 5-FU was not specific to NA cells, since ICAM-1 was synergistically induced by CDDP and 5-FU on HSC-4 cells, a squamous cell carcinoma cell line. These findings indicate that treatment with CDDP and 5-FU induces ICAM-1 expression by a NF-κB independent regulatory mechanism involving PTK. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00070920
Volume :
80
Issue :
7
Database :
Academic Search Index
Journal :
British Journal of Cancer
Publication Type :
Academic Journal
Accession number :
8876463
Full Text :
https://doi.org/10.1038/sj.bjc.6690449