Synergistic effect of CARM1 and PRMT6 inhibitors on the cell proliferation of WT MEFs.
A, WT MEFs were treated with a combination of the indicated concentration of CARM1 inhibitor (CARM1i) and PRMT6 inhibitor (PRMT6i) for a total of 6 days. At the end of the culture, cell counting was performed with the CellTiterGlo® kit, and the viabilities of different drug treatment groups were normalized by the group with no CARM1 inhibitor or PRMT6 inhibitor (which was set as 100%). B, normalized cell viabilities lower than 100% in A were allowed to be used to calculate the CI values, with CompuSyn software (ComboSyn, Inc., Paramus, NJ, USA). Synergistic interactions are implied by values of <1, whereas values of >1 indicate antagonistic interactions. C and D, WT MEFs were treated with 3 μm CARM1 inhibitor alone, 3 μm PRMT6 inhibitor alone, or the inhibitors combined for 6 days. The treated cells were stained with anti-γ-H2AX or DAPI to visualize the DNA damage foci in the nucleus (C) or lysed for Western blotting to detect the levels of γ-H2AX and H3R17me2a (D).