MET inhibition alone or in combination with PI3K/mTOR dual inhibitors induces cell cycle arrest and apoptosis.

<p>H2596 cells were treated with ARQ 197, GDC-0980, NVP-BEZ235 alone and in combination for 48 h. Cell cycle profile was determined using flow cytometry after staining with PI/RNase. <b>Fig.</b><b>A</b> shows the percentage of cells in G1, S, and G2/M phases was quantified and the results expressed as the mean ± SEM of four independent experiments. H2596 <b>(B)</b> and H513 <b>(C)</b> cells, were treated with ARQ 197, GDC-0980, NVP-BEZ235 alone and in combination for 48 h. Cell lysates were prepared and immunoblotted for total PARP, cleaved PARP, cyclin D1 and actin as a loading control. H2596 cells treated with ARQ 197, GDC-0980, NVP-BEZ235 alone and in combination for 48 h, the cells were then stained with Annexin V-FITC/PI and analyzed by flow cytometry. Results are expressed as mean percentage of apoptotic cells ± SEM of four independent experiments <b>(D)</b>.