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. 2016 Mar 15;6(4):714–746.

Figure 1.

Figure 1

Effect of BEZ235 and BEZ235 plus trastuzumab on proliferation assays: BT474, BT474HR, UACC893 and HCC1954 cells exhibit differential susceptibility to trastuzumab but are nearly equally sensitive to BEZ235. HCC1954 (HER2+, PIK3CAmutant [H1047R]) cell was particularly sensitive to this effect. Dose-response curves were obtained by MTT assay (A) after 48 hrs exposures of these four cell lines to BEZ235 (left panel) and the combination of Trastuzumab (10 µg/ml fixed dose) plus different doses of BEZ235 (right panel). Data clearly show that BEZ235 is highly effective in all four cell lines irrespective of PIK3CA mutation or not. (B) Representative clonogenic survival of HER2+/trastuzumab-sensitive (BT474) and HER2+/trastuzumab-resistant (BT474HerR) breast tumor cells were grown in the presence of trastuzumab (10 µg/ml) or BEZ235 (50 nM) or trastuzumab plus BEZ235. BT474 and BT474HerR cell lines were incubated with BEZ235, trastuzumab or a combination of trastuzumab plus BEZ235 for 48 hours and subsequently allowed to grow into colonies for both 96 hours and 7 days. Data clearly show as a single agent BEZ235 significantly inhibits cells growth as indicated by 2D and 3D assays at both 96 hours and 7 days. a: BT474, 2D assay at 96 hours, b: BT474, 2D assay at 7 days, c: BT474, 3D-ON-TOP clonogenic assay at 96 hours, d: BT474, 3D-ON-TOP clonogenic assay at 7 days, e: BT474HerR, 2D assay at 96 hours, f: BT474HerR, 2D assay at 7 days, g: BT474HerR, 3D-ON-TOP clonogenic assay at 96 hours, h: BT474HerR, 3D-ON-TOP clonogenic assay at 7 days. More importantly, the additive effect of the BEZ235 plus trastuzumab combination achieves a more powerful inhibition of clonogenic growth (both 2D and 3D-ON-TOP assays) than either agent in isolation.