Proteasome inhibitors decrease paclitaxelinduced cell death in nasopharyngeal carcinoma with the accumulation of CDK1/cyclin B1.
Int J Mol Med
; 48(4)2021 10.
Article
em En
| MEDLINE
| ID: mdl-34435645
ABSTRACT
Southeast Asia is a region with high incidence of nasopharyngeal carcinoma (NPC). Paclitaxel is the mainstay for the treatment of advanced nasopharyngeal cancer. The present study investigated the effect of proteasome inhibitors on the therapeutic effect of paclitaxel and its related mechanism. The present data from Cell Counting Kit8 and flow cytometry assays demonstrated that appropriate concentrations of proteasome inhibitors (30 nM PS341 or 700 nM MG132) reduced the lethal effect of paclitaxel on the nasopharyngeal cancer cells. While 400 nM paclitaxel effectively inhibited cell division and induced cell death, proteasome inhibitors (PS341 30 nM or MG132 700 nM) could reverse these effects. Additionally, the western blotting results demonstrated accumulation of cell cycle regulation protein CDK1 and cyclin B1 in proteasome inhibitortreated cells. In addition, proteasome inhibitors combined with paclitaxel led to decreased MCL1 apoptosis regulator, BCL2 family member/Caspase9/poly (ADPribose) polymerase apoptosis signaling triggered by CDK1/cyclin B1. Therefore, dysfunction of CDK1/cyclin B1 could be defining the loss of paclitaxel lethality against cancer cells, a phenomenon affirmed by the CDK1 inhibitor Ro3306. Overall, the present results demonstrated that a combination of paclitaxel with proteasome inhibitors or CDK1 inhibitors is antagonistic to effective clinical management of NPC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Nasofaríngeas
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Proteína Quinase CDC2
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Morte Celular
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Paclitaxel
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Ciclina B1
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Inibidores de Proteassoma
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Carcinoma Nasofaríngeo
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article