Gene expression profiling has revealed that the gene coding
for cannabinoid receptor 1 (CB1) is highly up-regulated
in rhabdomyosarcoma biopsies bearing the typical chromosomal
translocations PAX3/FKHR or PAX7/FKHR. Because
cannabinoid receptor agonists are capable of
reducing proliferation and inducing apoptosis in diverse
cancer cells such as glioma, breast cancer, and melanoma,
we evaluated whether CB1 is a potential drug target in
rhabdomyosarcoma. Our study shows that treatment with
the cannabinoid receptor agonists HU210 and Δ9
-tetrahydrocannabinol
lowers the viability of translocationpositive
rhabdomyosarcoma cells through the induction
of apoptosis. This effect relies on inhibition of AKT signaling
and induction of the stress-associated transcription
factor p8 because small interfering RNA–mediated
down-regulation of p8 rescued cell viability upon cannabinoid
treatment. Finally, treatment of xenografts with
HU210 led to a significant suppression of tumor growth
in vivo. These results support the notion that cannabinoid
receptor agonists could represent a novel targeted approach
for treatment of translocation-positive rhabdomyosarcoma.