Fig. 6.
The clinically used drugs BEZ235 and chloroquine cooperate to cause apoptosis in PTEN mt glioma cell lines. U373 PTENmt cells and cells derived from a PTEN mt xenograft of glioblastoma multiforme (GS2) were treated with the PI3K-mTOR inhibitor NVP-BEZ235 (BEZ) or the antimalarial autophagy and lysosomal trafficking inhibitor chloroquine (CQ) or both drugs. (A and B) BEZ and CQ cooperate to induce apoptosis (annexin V flow cytometry) in U373 and GS2 cells. Cells were treated with BEZ or vehicle (24 hours); CQ was then added where indicated (48 hours). (C to H) Dose response with single agents and effects of combination treatment in U373 and GS2 cells. The combination of BEZ and CQ induced apoptosis in both cell lines, whereas neither agent alone induced apoptosis (assessed by PARP cleavage). (C, D, F, and G) BEZ and CQ treatments were for 48 hours. (E and H) Treatments were as in (A) and (B).