Synergistic Effects of Arsenic Trioxide and Silibinin on Apoptosis and Invasion in Human Glioblastoma U87MG Cell Line

Patients with glioblastoma multiforme (GBM) have poor therapeutic outcomes despite their current therapy. In an attempt to increase the efficacy of therapy for GBM, we studied the efficacy of arsenic trioxide (ATO), a newly introduced treatment for glioma, combined with silibinin, a natural polyphenolic flavonoid, in the GBM cell line, U87MG. The combination therapy synergically inhibited metabolic activity, cell proliferation, and gelatinase A and B activities; it also increased apoptosis. Additionally, it decreased the mRNA level of cathepsin B, uPA, matrix metalloproteinase-2 and 9, membrane type 1-MMP, survivin, BCL2, CA9; it increased mRNA level of caspase-3. Altogether, these results showed that ATO and silibinin in some cases improved and/or complemented the anticancer effects. This study may supply insight into the design of new combination cancer therapies to cells intrinsically less sensitive to routine therapies and suggested a new combination therapy for the highly invasive human glioma treatment.