Oncogenic KRAS signaling mediates drug resistance and inhibits apoptosis. CCRF-HSB2 and U-937 cells stably transduced with either pLenti6.2-empty vector (EV) or pLenti6.2-KRASG13D (KRASG13D) were treated with (A) daunorubicin or (B) VP-16 as indicated. The fraction of apoptotic cells was determined by quantifying the sub-G1 fraction using flow cytometry. Data represent the mean values ± SD of 3 independent experiments (*P < .05, **P < .01, ***P < .001, Student t test). (C) Nomo-1 cells stably transduced with lentiviral vectors expressing a doxycycline-inducible nonsilencing miR-shRNA (sh ctrl) or a miR-shRNA targeting KRAS (sh KRAS) were treated with daunorubicin in the presence (black bars) or absence (white bars) of doxycycline. After 72 hours, the percentage of sub-G1 cells corresponding to apoptotic cells was determined by flow cytometry. Data represent the mean values ± SD of 3 independent experiments (**P < .01, Student t test). (D) Nomo-1 cells stably transduced with doxycycline-inducible sh ctrl or sh KRAS were treated with VP-16 in the presence (black bars) or absence (white bars) of doxycycline. After 48 hours, the percentage of sub-G1 cells corresponding to apoptotic cells was determined by flow cytometry. Data represent the mean values ± SD of 3 independent experiments (**P < .01, ***P < .001, Student t test).
