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Suppression of CD13 Enhances the Cytotoxic Effect of Chemotherapeutic Drugs in Hepatocellular Carcinoma Cells

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 o...

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Autores principales: Ji, Shengping, Ma, Yuqian, Xing, Xiaoyan, Ge, Binbin, Li, Yutian, Xu, Xinyue, Song, Jiliang, Xiao, Mei, Gao, Feng, Jiang, Wenyan, Fang, Chunyan, Wang, Xuejian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144446/
https://www.ncbi.nlm.nih.gov/pubmed/34045966
http://dx.doi.org/10.3389/fphar.2021.660377
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author Ji, Shengping
Ma, Yuqian
Xing, Xiaoyan
Ge, Binbin
Li, Yutian
Xu, Xinyue
Song, Jiliang
Xiao, Mei
Gao, Feng
Jiang, Wenyan
Fang, Chunyan
Wang, Xuejian
author_facet Ji, Shengping
Ma, Yuqian
Xing, Xiaoyan
Ge, Binbin
Li, Yutian
Xu, Xinyue
Song, Jiliang
Xiao, Mei
Gao, Feng
Jiang, Wenyan
Fang, Chunyan
Wang, Xuejian
author_sort Ji, Shengping
collection PubMed
description 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 in vitro and in vivo. In general, overexpression of CD13 can lead to chemotherapy resistance, and CD13 inhibitor can reverse this effect. Combination of chemotherapy agent and ubenimex will become a potential treatment strategy for liver cancer resistance.
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spelling pubmed-81444462021-05-26 Suppression of CD13 Enhances the Cytotoxic Effect of Chemotherapeutic Drugs in Hepatocellular Carcinoma Cells Ji, Shengping Ma, Yuqian Xing, Xiaoyan Ge, Binbin Li, Yutian Xu, Xinyue Song, Jiliang Xiao, Mei Gao, Feng Jiang, Wenyan Fang, Chunyan Wang, Xuejian Front Pharmacol Pharmacology 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 in vitro and in vivo. In general, overexpression of CD13 can lead to chemotherapy resistance, and CD13 inhibitor can reverse this effect. Combination of chemotherapy agent and ubenimex will become a potential treatment strategy for liver cancer resistance. Frontiers Media S.A. 2021-05-11 /pmc/articles/PMC8144446/ /pubmed/34045966 http://dx.doi.org/10.3389/fphar.2021.660377 Text en Copyright © 2021 Ji, Ma, Xing, Ge, Li, Xu, Song, Xiao, Gao, Jiang, Fang and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Ji, Shengping
Ma, Yuqian
Xing, Xiaoyan
Ge, Binbin
Li, Yutian
Xu, Xinyue
Song, Jiliang
Xiao, Mei
Gao, Feng
Jiang, Wenyan
Fang, Chunyan
Wang, Xuejian
Suppression of CD13 Enhances the Cytotoxic Effect of Chemotherapeutic Drugs in Hepatocellular Carcinoma Cells
title Suppression of CD13 Enhances the Cytotoxic Effect of Chemotherapeutic Drugs in Hepatocellular Carcinoma Cells
title_full Suppression of CD13 Enhances the Cytotoxic Effect of Chemotherapeutic Drugs in Hepatocellular Carcinoma Cells
title_fullStr Suppression of CD13 Enhances the Cytotoxic Effect of Chemotherapeutic Drugs in Hepatocellular Carcinoma Cells
title_full_unstemmed Suppression of CD13 Enhances the Cytotoxic Effect of Chemotherapeutic Drugs in Hepatocellular Carcinoma Cells
title_short Suppression of CD13 Enhances the Cytotoxic Effect of Chemotherapeutic Drugs in Hepatocellular Carcinoma Cells
title_sort suppression of cd13 enhances the cytotoxic effect of chemotherapeutic drugs in hepatocellular carcinoma cells
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144446/
https://www.ncbi.nlm.nih.gov/pubmed/34045966
http://dx.doi.org/10.3389/fphar.2021.660377
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