The PARP1 Inhibitor Niraparib Represses DNA Damage Repair and Synergizes with Temozolomide for Antimyeloma Effects

Figure 6

The TMZ/Nira regimen suppresses plasmacytoma xenograft in vivo. (a) Human MM cell-derived xenograft model was built using RPMI8226 cells to confirm the synergistic effects of TMZ and Nira. The animals had decreased tumor volumes upon administration of the TMZ-Nira combination compared with the TMZ and Nira monotherapy and control groups. (b, c) Tumor size and weight measurements revealed decreased plasmacytoma xenograft growth after TMZ/Nira cotreatment. (d) The percentages of TUNEL-positive cells were obtained by ImageJ. (e) Apoptotic and proliferating cells in tumor specimens, respectively, were detected by the TUNEL assay, H&E staining, and immunochemistry. The expression levels of γH2A.X, RAD51, Ki67, and cleaved caspase-3 were determined by immunohistochemistry. Reduced expression of Ki67 and elevated expression of γH2A.X, RAD51, and cleaved caspase-3 were found in the TMZ plus Nira group. ( per group). Significant differences were indicated as follows: , , , and versus control group; ^### versus TMZ group; ⁺⁺⁺ versus Nira group. Scale bar, 20 μm. Original magnification, ×400. TMZ: temozolomide; Nira: niraparib.

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