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Tetrahydrobiopterin induces proteasome inhibitor resistance and tumor progression in multiple myeloma.
Zhang, Hua; Chen, Jintong; Zhang, Mingyue; Zhao, Munan; Zhang, Luyao; Liu, Bin; Wang, Siqing.
Afiliação
  • Zhang H; Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, 130021, China.
  • Chen J; Department of Cancer Immunology, The First Hospital of Jilin University, 519 Dongminzhu St, Changchun, 130061, Jilin, China.
  • Zhang M; Department of Gynecological Oncology, The First Hospital of Jilin University, Changchun, 130021, China.
  • Zhao M; Department of Cancer Center, The First Hospital of Jilin University, Changchun, 130021, China.
  • Zhang L; Department of Gastrointestinal Surgery, The First Hospital of Jilin University, Changchun, 130021, China.
  • Liu B; Department of Hand and Foot Surgery, The First Hospital of Jilin University, 71 Xinmin St, Changchun, 130021, Jilin, China. l_bin@jlu.edu.cn.
  • Wang S; Department of Cancer Immunology, The First Hospital of Jilin University, 519 Dongminzhu St, Changchun, 130061, Jilin, China. wkerger@jlu.edu.cn.
Med Oncol ; 39(5): 55, 2022 Feb 12.
Article em En | MEDLINE | ID: mdl-35150316
Multiple myeloma (MM) still remains an incurable disease due to widespread drug resistance and high frequency of relapse. In this study, we found that tetrahydrobiopterin (BH4) promotes MM cell proliferation and tumor growth in vivo. BH4 also increases MM bortezomib (Bor) resistance in vitro and in vivo. We show that BH4 increases the expressions of USP7 and USP46 in MM cells, which are responsible for MM Bor resistance primed by BH4. BH4 promotes the degradation of P53 and the activation of NF-κB signaling through the up-regulation of USP7 and USP46. Furthermore, the inhibition of USPs increases the therapeutic effects of Bor in MM tumor bearing mice. Our results demonstrate the important role of BH4 in MM Bor resistance and tumor progression in vivo. These findings could potentially have clinical implications.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biopterinas / Resistencia a Medicamentos Antineoplásicos / Inibidores de Proteassoma / Peptidase 7 Específica de Ubiquitina / Mieloma Múltiplo Limite: Animals / Humans Idioma: En Revista: Med Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Biopterinas / Resistencia a Medicamentos Antineoplásicos / Inibidores de Proteassoma / Peptidase 7 Específica de Ubiquitina / Mieloma Múltiplo Limite: Animals / Humans Idioma: En Revista: Med Oncol Assunto da revista: NEOPLASIAS Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China País de publicação: Estados Unidos