Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1
Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1
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DOI：
10.1096/fj.11-198184
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发表时间：
2012-04-01
期刊：
影响因子：
4.8
通讯作者：
Hinz, Burkhard
中科院分区：
文献类型：
--
作者：
Ramer, Robert;Bublitz, Katharina;Hinz, Burkhard
Cannabinoids inhibit cancer cell invasion via increasing tissue inhibitor of matrix metallo-proteinases-1 (TIMP-1). This study investigates the role of intercellular adhesion molecule-1 (ICAM-1) within this action. In the lung cancer cell lines A549, H358, and H460, cannabidiol (CBD; 0.001-3 mu M) elicited concentration-dependent ICAM-1 up-regulation compared to vehicle via cannabinoid receptors, transient receptor potential vanilloid 1, and p42/44 mitogen-activated protein kinase. Up-regulation of ICAM-1 mRNA by CBD in A549 was 4-fold at 3 mu M, with significant effects already evident at 0.01 mu M. ICAM-1 induction became significant after 2 h, whereas significant TIMP-1 mRNA increases were observed only after 48 h. Inhibition of ICAM-1 by antibody or siRNA approaches reversed the anti-invasive and TIMP-1-upregulating action of CBD and the likewise ICAM-1-inducing cannabinoids Delta(9)-tetrahydrocannabinol and R(+)-methanandamide when compared to isotype or nonsilencing siRNA controls. ICAM-1-dependent antiinvasive cannabinoid effects were confirmed in primary tumor cells from a lung cancer patient. In athymic nude mice, CBD elicited a 2.6- and 3.0-fold increase of ICAM-1 and TIMP-1 protein in A549 xenografts, as compared to vehicle-treated animals, and an antimetastatic effect that was fully reversed by a neutralizing antibody against ICAM-1 [% metastatic lung nodules vs. isotype control (100%): 47.7% for CBD + isotype antibody and 106.6% for CBD + ICAM-1 antibody]. Overall, our data indicate that cannabinoids induce ICAM-1, thereby conferring TIMP-1 induction and subsequent decreased cancer cell invasiveness.-Ramer, R., Bublitz, K., Freimuth, N., Merkord, J., Rohde, H., Haustein, M., Borchert, P., Schmuhl, E., Linnebacher, M., Hinz, B. Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule- 1. FASEB J. 26, 1535-1548 (2012). www.fasebj.org
