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

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 immunob...

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Autores principales: Shi, Yuanfei, Ye, Jing, Shen, Huafei, Xu, Yi, Wan, Rui, Ye, Xiujin, Jin, Jie, Xie, Wanzhuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580892/
https://www.ncbi.nlm.nih.gov/pubmed/36053810
http://dx.doi.org/10.1002/1878-0261.13309
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author Shi, Yuanfei
Ye, Jing
Shen, Huafei
Xu, Yi
Wan, Rui
Ye, Xiujin
Jin, Jie
Xie, Wanzhuo
author_facet Shi, Yuanfei
Ye, Jing
Shen, Huafei
Xu, Yi
Wan, Rui
Ye, Xiujin
Jin, Jie
Xie, Wanzhuo
author_sort Shi, Yuanfei
collection PubMed
description 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.
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spelling pubmed-95808922022-10-20 Apatinib enhances chemosensitivity of ABT‐199 in diffuse large B‐cell lymphoma Shi, Yuanfei Ye, Jing Shen, Huafei Xu, Yi Wan, Rui Ye, Xiujin Jin, Jie Xie, Wanzhuo Mol Oncol Research Articles 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. John Wiley and Sons Inc. 2022-09-07 2022-10 /pmc/articles/PMC9580892/ /pubmed/36053810 http://dx.doi.org/10.1002/1878-0261.13309 Text en © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Shi, Yuanfei
Ye, Jing
Shen, Huafei
Xu, Yi
Wan, Rui
Ye, Xiujin
Jin, Jie
Xie, Wanzhuo
Apatinib enhances chemosensitivity of ABT‐199 in diffuse large B‐cell lymphoma
title Apatinib enhances chemosensitivity of ABT‐199 in diffuse large B‐cell lymphoma
title_full Apatinib enhances chemosensitivity of ABT‐199 in diffuse large B‐cell lymphoma
title_fullStr Apatinib enhances chemosensitivity of ABT‐199 in diffuse large B‐cell lymphoma
title_full_unstemmed Apatinib enhances chemosensitivity of ABT‐199 in diffuse large B‐cell lymphoma
title_short Apatinib enhances chemosensitivity of ABT‐199 in diffuse large B‐cell lymphoma
title_sort apatinib enhances chemosensitivity of abt‐199 in diffuse large b‐cell lymphoma
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580892/
https://www.ncbi.nlm.nih.gov/pubmed/36053810
http://dx.doi.org/10.1002/1878-0261.13309
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