Apatinib enhances chemosensitivity of ABT‐199 in diffuse large B‐cell lymphoma

Abstract

To investigate the effect of Apatinib (an inhibitor targeting VEGFR‐2) enhances chemosensitivity of ABT‐199 on diffuse large B‐cell lymphoma (DLBCL). Viability assay and flow cytometric assay for determining apoptosis, cell cycle, mitochondrial membrane potential, reactive oxygen species and immunoblotting were used to explore the combination effect in DLBCL cell lines, DLBCL patient samples, and DLBCL mouse models. RNA sequencing assay helped identify mechanisms of ABT‐199 plus Apatinib. The results show that 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 tumour cell growth and promoted tumour 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. Our findings indicate that Apatinib enhances the chemosensitivity of ABT‐199 and might serve as a promising therapeutic strategy for DLBCL.

Keywords

• ABT‐199
• Apatinib
• DLBCL
• EDN1
• MAPK
• VEGFR‐2