Fig. 4

Simultaneous reduction of p110α and Vps34 reduces proliferation and sensitizes human epidermal growth factor receptor-2 positive (HER2+) cells to lapatinib. UACC893, BT474 and SKBR3 cells were transfected with siRNA at a final concentration of 100 nM, 50 nM each: 1) siCTRL + siCTRL (CTRL); 2) siVps34 + siCTRL(V34); 3) sip110α + siCTRL(p110); 4) siVps34 + sip110α (V + p). Three days post-transfection, cells were treated with dimethyl sulfoxide (DMSO) control or 1 μM lapatinib (Lap). a Relative cell number was assessed 24 h after lapatinib treatment by sulforhodamine B assay. Within each drug treatment (DMSO or Lap): *p <0.05 comparing siCTRL + siCTRL to the other three combinations; #p <0.05 comparing single targeted siRNA to siVps34 + sip110; one way analysis of variance with Tukey multiple comparison test. Student t test analysis of each DMSO/lapatinib pair was significant (p <0.05), and is not graphically depicted. b Lysates were harvested 2 h after lapatinib treatment and were analyzed by immunoblot with the indicated antibodies. PARP poly(ADP-ribose) polymerase, C Casp 3 cleaved caspase 3