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Journal of Zhejiang University. Science. B ; (12): 442-454, 2023.
Artigo em Inglês | WPRIM | ID: wpr-982384

RESUMO

CUDC-101, an effective and multi-target inhibitor of epidermal growth factor receptor (EGFR), histone deacetylase (HDAC), and human epidermal growth factor receptor 2 (HER2), has been reported to inhibit many kinds of cancers, such as acute promyelocytic leukemia and non-Hodgkin's lymphoma. However, no studies have yet investigated whether CUDC-101 is effective against myeloma. Herein, we proved that CUDC-101 effectively inhibits the proliferation of multiple myeloma (MM) cell lines and induces cell apoptosis in a time- and dose-dependent manner. Moreover, CUDC-101 markedly blocked the signaling pathway of EGFR/phosphoinositide-3-kinase (PI3K) and HDAC, and regulated the cell cycle G2/M arrest. Moreover, we revealed through in vivo experiment that CUDC-101 is a potent anti-myeloma drug. Bortezomib is one of the important drugs in MM treatment, and we investigated whether CUDC-101 has a synergistic or additive effect with bortezomib. The results showed that this drug combination had a synergistic anti-myeloma effect by inducing G2/M phase blockade. Collectively, our findings revealed that CUDC-101 could act on its own or in conjunction with bortezomib, which provides insights into exploring new strategies for MM treatment.


Assuntos
Humanos , Antineoplásicos/uso terapêutico , Apoptose , Bortezomib/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Receptores ErbB/antagonistas & inibidores , Pontos de Checagem da Fase G2 do Ciclo Celular , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Células M , Mieloma Múltiplo/tratamento farmacológico
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