Fig. 6

EZH2 inhibition suppressed the growth of CARM1-expressing tumors in vivo and improved the survival of mice bearing CARM1-expressing tumors. a CARM1-high A1847 ovarian cancer cells were unilaterally injected into the ovarian bursa sac of immunocompromised mice (n = 5/group). Tumors were allowed to establish for 1 week before the mice were randomized into two different treatment groups. Mice were treated with vehicle control or GSK126 (50 mg/kg daily) for an additional 3 weeks. At the end of treatment, the mice were euthanized. Shown are images of reproductive tracts with tumors from control or GSK126-treated mice. Bar = 1 cm. b Tumor weight was measured as a surrogate for tumor burden from the control and GSK126-treated mice. c After stopping the treatment, the mice from the indicated groups were followed for survival. Shown is the Kaplan–Meier survival curve for GSK126 or vehicle-treated mice. P-value was calculated by log-rank test. d The serial sections of tumors dissected from the indicated treatment groups were subjected to immunohistochemical staining for H3K27Me3, EZH2, cleaved caspase 3, and Ki67. Scale bar = 50 μm. e Histological score (H-score) of the indicated proteins was calculated for three separate fields from five tumors from five individual mice from each of the indicated groups. f Expression of the indicated EZH2/BAF155 target genes was determined by qRT-PCR in the tumors dissected from the indicated treatment groups. g CARM1 regulates the antagonism between SWI/SNF and PRC2 through methylating BAF155. EZH2 inhibition reactivates EZH2/BAF155 target tumor suppressive genes to promote apoptosis, inhibit proliferation, and suppress tumor growth. Error bars represent SEM. P-values are from two-tailed t-test