A subset of mesothelioma cells is sensitive to GDC-0980.

<p>(A) M28 and REN monolayers and spheroids were treated with GDC-0980 (1 μM), bortezomib (25 nM), cisplatin (200 μM) plus pemetrexed (10 μM)(C+P) or the combinations for 24 h. Cells with condensed nuclei seen after Hoechst staining were considered apoptotic <i>(* p</i> < <i>0</i>.<i>05</i> compared to the same treatment without GDC-0980; <i>n</i> = 3; mean ± SD). In the spheroids, GDC-0980 had activity when given alone and significantly potentiated chemotherapy in M28 cells but not in REN cells. (B) CaspaseGlo on M28 and REN spheroids treated as previously for 16 h. Caspase 3/7 activation is expressed as relative luminescence units (RLUx10⁵). Again, M28 cells demonstrated sensitivity to GDC-0980 and REN cells demonstrated resistance. <i>(* p</i> < <i>0</i>.<i>05</i> compared to the same treatment without GDC-0980; <i>n</i> = 3; mean ± SD). (C) Six cell lines (M28, SARC, VAMT, REN, JMN, MSTO-211H) grown as spheroids were treated with GDC-0980 (1 μM), bortezomib (25 nM) or the combination for 24 h. Three cell lines showed a response to GDC-0980 (<i>sensitive</i>) and 3 showed no response (<i>resistant</i>). <i>(* p</i> < <i>0</i>.<i>05</i> compared to the same treatment without GDC-0980; <i>n</i> = 3; mean ± SD) (D) Caspase 3/7 activation in spheroids treated similarly for 16 h, measured by CaspaseGlo, confirmed the differences between the sensitive and resistant spheroids. <i>(* p</i> < <i>0</i>.<i>05</i> different from the response to chemotherapy alone; <i>n</i> = 3; mean ± SD) (E) M28 spheroids were treated with higher concentrations of GDC-0980 (1,10 and 20 μM) for 24 h and caspase 3/7 activity was measured by CaspaseGlo. Higher concentrations of GDC-0980 did not increase its efficacy.