Visit our Expo - Redox and Inflammation signaling 2012

Session IX. Novel compounds targeting inflammatory signaling pathways Poster IX, 5
Inhibition of ICAM-1-mediated metastasis by thalidomide in human lung cancer
Yi-Chu Lin and Ching-Chow Chen
Department of Pharmacology, College of Medicine, National Taiwan University,
Taipei 10018, Taiwan. E-Mail: f92443016@ntu.edu.tw
Our previous study demonstrated that TNF-alpha-induced expression of Intercellular
Adhesion Molecule-1 (ICAM-1) not only increased monocyte adherence to the lung epithelial
cells, but also elicited tumor cell invasion. In this report, we examined the role of ICAM-1 in
carcinogenesis and the effect of thalidomide. The in vitro cell invasion and the in vivo tumor
metastasis induced by ICAM-1-overexpressing A549 cells were both inhibited by
thalidomide. The tumors grown in nude mice induced by s.c. human lung cancer xenografts
were detected to express ICAM-1 and attenuated by oral administration of thalidomide (200
microg/kg/day). Moreover, highly expressed ICAM-1 was detected in the human specimens
of lung cancer patients. The inhibitory effect of thalidomide on the TNF-alpha-induced
protein and mRNA expressions of ICAM-1 was seen, and this inhibition attributed to the
reduced activity and binding of NF-kappaB to the ICAM-1 promoter. However, IkappaBalpha
degradation and translocation of NF-kappaB to the nucleus were not affected by
thalidomide. These studies provide a framework for targeting ICAM-1 gene by thalidomide as
a biologically based therapy for lung cancer.
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