(A) 4 × 4 grids with combinatorial inhibitor titrations to test for the synergy of PI3K inhibition by BKM120 (left) or XL147 (right) with vincristine (VCR) in JURKAT cells.
(B) Single and combinatorial titration of GDC0941 and VCR in 3-day growth assay (top), and cell growth overtime with 1 μM GDC0941 and 1.2 nM VCR alone or in combination (bottom).
(C) Flow cytometric analysis of JURKAT treated with 1 μM DXR alone or 3 μM GDC0941 and a titration of VCR at 1.6, 2.4, and 3.6 nM, alone or in combination; stained for apoptotic cells with annexin V and dead cells with propidium iodide.
(D) Flow cytometric analysis of JURKAT cells treated with 3 μM GDC0941 and 2.4 nM VCR, alone or in combination; stained for (i) markers of cell proliferation, (ii) anti-apoptotic proteins, (iii) mitotic arrest indicators, (iv) apoptosis induction cascade, and (v) mitochondrial membrane potential.
(E) Schematic representation of mechanisms for the combinatorial efficacy of PI3K and tubulin inhibition.
(A)–(D) are representative examples of ≥3 independent experiments.