The Bulletín of Kanagawa Dental College

Vol. 36 No. 2       September- 2008

ISSN: 0385-1443      UBIC: 65

ABSTRACT

The chemokine BRAK/CXCL14 is expressed in many normal cells, but absent or expressed at very low levels in transformed cells and cancerous tissues including oral carcinoma. We reported previously that BRAK had suppressive activity toward tumor progression of oral carcinoma in vivo when over-expressed in tumor cells. Oral administration of gefitinib (Iressa, ZD1839), an anti-tumor drug developed for molecular targeting therapy for the epidermal growth factor receptor, significantly reduced tumor volumes with a restorative increase in BRAK mRNA expression. In order to investigate the mechanisms of the tumor suppression in vivo, we xenografted nude mice with HSC-3 cells that had been transfected with control Si-scrambled vector or síRNA of BRAK to down-regulate the BRAK mRNA expression. Oral administration of gefitinib inhibited the proliferation of the tumor cells transfected with either Si-scrambled or Si-BRAK vector. But the increase in apoptosis initiated by gefitinib was significantly reduced in the case of tumor cells transfected with Si-BRAK. These results suggest that BRAK stimulates apoptosis initiated by gefitinib. Key words: BRAK / CXCLI4 / chemokine / gefitinib / epidermal growth factor receptor.

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