Suppression of CD13 Enhances the Cytotoxic Effect of Chemotherapeutic Drugs in Hepatocellular Carcinoma Cells.
CD13
ROS
heptaocellular carcinoma
multidrug resistance
ubenimex
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2021
2021
Historique:
received:
29
01
2021
accepted:
27
04
2021
entrez:
28
5
2021
pubmed:
29
5
2021
medline:
29
5
2021
Statut:
epublish
Résumé
Multidrug resistance (MDR) of hepatocellular carcinoma (HCC) is a serious problem that directly hinders the effect of chemotherapeutics. In this study, we mainly explore the molecular mechanism of ROS-induced CD13 expression using hepatocarcinoma cells as the research object. We show that the drug of fluorouracil (5FU), epirubicin (EPI) and gemcitabine (GEM) can induce ROS generation, activate Ets2 and promote CD13 expression. Meanwhile, CD13 can activate NRF1 and up-regulate ROS scavenging genes transcription, such as SOD1, GPX1, GPX2 and GPX3, leading to down-regulation of intracellular ROS level and reducing the sensitivity of cells to chemotherapy agent. We also detected the anti-tumor effect of the combination therapy, CD13 inhibitor ubenimex and a variety of conventional anti-cancer drugs, such as 5FU, EPI, GEM, pemetrexed (Pem) and paclitaxel (PTX) were employed in combination. Ubenimex enhances the sensitivity of different chemotherapeutic agents and cooperates with chemotherapeutic agents to suppress tumor growth
Identifiants
pubmed: 34045966
doi: 10.3389/fphar.2021.660377
pii: 660377
pmc: PMC8144446
doi:
Types de publication
Journal Article
Langues
eng
Pagination
660377Informations de copyright
Copyright © 2021 Ji, Ma, Xing, Ge, Li, Xu, Song, Xiao, Gao, Jiang, Fang and Wang.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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