Abstract
Thalidomide and 13‐cis retinoic acid (RA) show anticancer effects as sole agents or in combination with other drugs. However, induction of homeobox (HOX) gene expression by 13‐cis RA may contribute to tumor progression thereby potentially limiting its efficacy. The purpose was to test if thalidomide can inhibit 13‐cis RA‐induced HOXB7 expression and whether thalidomide may enhance the antiproliferative effect of 13‐cis RA in U343MG glioblastoma cells. Quantitative real‐time PCR showed significant inhibition of 13‐cis RA‐induced HOXB7 expression by thalidomide with IC~50~ ∼ 0.1–0.2 μg/ml when given simultaneously with 13‐cis RA but not when administered 18h later (p < 0.0001). 13‐cis RA alone inhibited proliferation and colony formation in a concentration‐dependent manner whereas growth inhibition by thalidomide alone at 5–100 μg/ml was constant at 80–90% of controls. At 10% serum concentration, growth inhibition by a combination of the 2 drugs was additive but at 1% serum, growth inhibition was synergistic. It is concluded that thalidomide inhibits the RA‐induced HOXB7 expression in glioblastoma cells and that 13‐cis RA/thalidomide combinations can in principle enhance cytotoxicity. The improved cell kill induced by thalidomide is attributed to downregulation of growth stimulatory factors induced by 13‐cis RA. Implications for the modus operandi of thalidomide in embryogenesis are noted. © 2007 Wiley‐Liss, Inc.