Figure 5.
The synergistic effect of the combination of talazoparib with romidepsin is mediated via Blimp1. (A) Venn diagram. (B) Smear plot of transcriptional changes after talazoparib plus romidepsin demonstrates selected genes presented in all 3 groups. (C) The transcriptional changes in DNA repair, cell cycle arrest, and apoptosis pathways in MBL2 cells treated with talazoparib and romidepsin. (D) Western blots for expression of proteins MDM2, MDM4, CDC2, p53, p21, and G6PD from MBL2 cells without treatment (C) or treated with romidepsin (R), talazoparib (T), or romidepsin plus talazoparib (R+T). (E-F) The Blimp-1 expression after treatment. Representative flow (E) and statistical analysis (F). ****P < .001. (G) FPKM of IRF8, BCL6, IRF4, PRDM1, BCL2L11, and BAX after treatment with romidepsin (R), talazoparib (T), and romidepsin plus talazoparib (R+T). MBL2 cells without any treatment were used as controls (C). RNASeq. *P < .05, **P < .01, ***P < .001, ****P < .0001. (H) Corresponding western blots of proteins after treatment with romidepsin (R), talazoparib (T), and romidepsin plus talazoparib (R+T). (I) Proposed schema of activation of apoptosis during the combination therapy with romidepsin and talazoparib.