Combination therapy with micellarized cyclopamine and temozolomide attenuate glioblastoma growth through Gli1 down-regulation.

摘要: Glioblastoma multiforme (GBM) is the most common and deadly brain cancer, characterized by its aggressive proliferation to adjacent tissue high recurrence rate. We studied efficacy related mechanisms of combination cyclopamine (Cyp, a Sonic-hedgehog pathway (Shh) inhibitor) temozolomide (TMZ, clinically used chemotherapeutic agent) in anti-GBM treatment. The micellarized Cyp (MCyp) showed better performance than solution inhibiting GBM cells (3.77-fold against U87 MG 3.28-fold DBTRG-05MG cells) clonogenity (1.35-fold 2.17-fold cells), preferred behavior cell invasion, colony formation through attenuated Gli1 expression. In addition, MCyp TMZ exhibited synergistic cytotoxicity, correlating with their ability inducing apoptosis eliminating neurospheres formation, was accompanied enhanced blockage Shh pathway. optimal ratio combined 1:20. So we proposed use kill tumor parenchyma as cancer stem inhibitor resist recurrence. These findings demonstrated that promising strategy for exerting different functions drugs