Figure 6.

Carcinogenic microenvironment enables A1207 p110γ-dependent tumor growth. (A–E) 4NQO carcinogenesis and treatment regimen: mice received 50 µg/mL 4NQO in the drinking water (or regular drinking water for control mice) for 16 weeks and returned to regular drinking water thereafter. Mice received daily IPI549 or vehicle treatments beginning week 15 for the duration of the experiment and all mice were transplanted with A1207 cells to the dorsal tongue on week 16. (B) Representative images of whole tongue sections from mice treated with water versus 4NQO+IPI549 versus 4NQO+Vehicle all transplanted with A1207 cells on week 16. Black dotted line outlines the tumor border. (C) Tumor volume in each treatment group was determined. *p<0.05, **p<0.01, **p<0.001 determined by one-way ANOVA with Tukey’s multiple comparison test (right). (D–E) Ly6G immunostaining and quantification of tongue tumors. *p<0.05 determined by unpaired Student’s t-test. (F–H) C57BL/6 mice were transplanted with A1206 tumor cells to the right flank or not transplanted. When A1206 tumors reached 300 mm³, all mice (naïve and A1206 tumor-bearing) were transplanted with A1207 cells to the left flank. (G) Size of left flank A1207 tumor was monitored over time. Due to the size of A1206 tumors, all mice required euthanasia 34 days after A1207 transplant. **p<0.01 determined by unpaired Student’s t-test at the indicated time points. (H) Rate of complete A1207 tumor clearance was monitored over time. *p<0.05 determined by log-rank test. ANOVA, analysis of variance; wk, week; 4NQO, 4-nitroquinoline 1-oxide.