Figure 4.

PTEN-negative, E-cadherin-low UBC cells are sensitive to PIK3CB depletion. a. To generate xenografts, 639V cells were injected subcutaneously into immunodeficient mice. When tumors reached 75 mm³, mice were treated by i.t. injection of PBS (control), vehicle alone (Invivofectamine, liposomes), or vehicle plus control or siPIK3CB (50pmol/mm³), every other day for two weeks. b. Xenografts were generated as in a. using 639V cells expressing doxycycline (Doxy)-inducible PIK3CB shRNA. When tumors reached ~75 mm³, ~half of the mice were treated by addition of Doxy (4 mg/ml) in the drinking water. c. Another set of tumors was generated similarly and was treated by i.p. injection of AZD8186 (40 mg/kg) in vehicle (methylcellulose) or with vehicle alone (control) every 12 h (days 1 to 5 each week) and once a day (days 6 and 7) for two weeks. (a-c) Graphs show the x-fold increase in tumor size (mean ± SD) at various times relative to volume at treatment initiation (day 1). *** P < 0.001; ** P < 0.01; * P < 0.05; n.s. not significant; one-way ANOVA, Tukey's comparison test. d. WB analysis of extracts from representative tumors (a-c). e. Hematoxylin/eosin staining of representative tumors from a..