Fig. 7

WIP1 and PARP inhibition induce synthetic lethality of HCC cells in vivo. Xenograft model (n = 7 per group) was generated by subcutaneous inoculation of PLC/PRF/5 cells. Mice were then treated with Olaparib and GSK2830371 as indicated. Tumor pictures (A), tumor growth curve (B) and tumor weight (C) were summarized and shown respectively. Veliparib and GSK2830371 combination treatment experiment was performed as above, and tumor pictures (D), tumor growth curve (E) and tumor weight (F) were summarized and shown respectively. C-PARP1 and γH2AX in tumor tissues were evaluated by Western blotting, Olaparib and GSK2830371 combination in (G), Veliparib and GSK2830371 combination in (H). I–J The ki-67 immunohistochemical staining of tumor tissues with indicated treatment was shown. K Working model. WIP1 functions as a homeostatic regulator during DNA double strand break by de-phosphorylating γH2AX at the end of DNA damage repair. Thus, co-targeting WIP1 and PARP could induce HCC synthetic lethality via disrupting DNA damage repair, which likes the PARPi works in BRCA1/2 deficient cancers