Figure 5: Pharmacological BCL-2 inhibition reduces tumor initiation.

(a) Representative bright field images of untreated (left) and BCL-2 inhibitor (ABT-199) treated (right) organoid structures obtained from Lgr5.Apc^+/+ (top) and Lgr5.Apc^fl/fl (bottom) mice 5 days after induction with tamoxifen. Scale bar, 50 μM. (b) Graphs depict the relative outgrowth of structures 7 days after passaging for the indicated genotype and ABT-199 dose at time of induction. Each dot represents a replicate (minimal n=5 per condition), error bars indicate the s.e.m. **P<0.01, ***P<0.001, Student’s t-test. (c) Graph depicting the relative outgrowth of Apc^−/− structures 7 days after passaging treated with BCL-XL inhibitor (WEHI-539, 1,000 nM) at time of induction. Each dot represents a replicate (minimal n=5 per condition), error bars indicate the s.e.m. NS, not significant, Student’s t-test. (d) Representative H&E images of sections of the small intestine of Lgr5.Apc^fl/fl mice, which were killed at day 27 post induction. The ABT-199 treated cohort received 100 mg kg⁻¹ ABT-199 starting 2 days before induction for three consecutive days followed by administration every other day until day 27. Scale bars, 2 mm. (e) Graph displaying the number of adenomas at day 27 post induction. Each dot represents a mouse (minimal n=4 per condition), error bars represent the s.e.m. *P<0.05, Student’s t-test. (f) Plot showing the quantification of the fraction of cyst-like structures in control and ABT-199 treated mice. Each dot represents a mouse (minimal n=3 per condition), error bars represent the s.e.m. ***P<0.001, Student’s t-test.