Arsenic Trioxide Inhibits Tumor Cell Growth in Malignant Rhabdoid Tumor Cell In Vitro and In Vivo by Targeting Overexpressed Gli1

Abstract

Sonic hedgehog pathway (SHH) has been implicated in tumorigenesis and maintenance of tumor progenitor cells. In a subgroup of rhabdoid tumors SHH is activated downstream of the receptors smo and ptch. SMARCB1/INI1 directly controls the expression of Gli1 indicating that loss of INI1 may induce deregulation of Gli1. Small molecular inhibitors specifically targeting Gli1 (e.g. GANT 61), have been evaluated in preclinical studies, but are not available for clinical purposes yet. Arsenic trioxide targets Gli expression and inhibits proliferation of smo-receptor resistant SHH-activated medulloblastoma in vitro and in vivo.