Synergistic Lethality Effects of ABT-199 and Apatinib on DLBCL: Antitumor Efficacy and Underlying Mechanisms

Abstract Background To investigate the effect of ABT-199 combined with Apatinib on diffuse large B-cell lymphoma (DLBCL). Methods We explored the synergistic effect of ABT-199 and Apatinib in diffuse large B-cell lymphoma (DLBCL) cell lines, DLBCL patient samples, and DLBCL mouse models, using viability assay and immunoblotting. RNA sequencing assay helped identify mechanisms of ABT-199 plus Apatinib. Results ABT-199 combined with Apatinib inhibited cell proliferation, reduced colony-forming capacity, and induced apoptosis and cell cycle arrest in DLBCL cells. Mechanistically, the combination therapy inhibited tumor cell growth and promoted tumor cell death by regulating EDN1 and MAPK related pathways and activating the intrinsic apoptotic pathway. The effect of the combination therapy was also validated in primary DLBCL blasts and xenograft mouse models. Conclusion Our findings indicate that simultaneously targeting both BCL-2 and VEGFR2 might serve as a promising therapeutic strategy for DLBCL.