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Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells
Hepatocellular carcinoma (HCC) is one of the most serious cancers, with rapid progression and high mortality. However, chemotherapy of HCC is hindered by multi-drug resistance (MDR). It is urgent, therefore, to explore new approaches for overcoming MDR of HCC cells. Ubenimex, an inhibitor of CD13, h...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641159/ https://www.ncbi.nlm.nih.gov/pubmed/29069816 http://dx.doi.org/10.18632/oncotarget.20194 |
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author | Guo, Qie Sui, Zhong-Guo Xu, Wen Quan, Xiang-Hua Sun, Jia-Lin Li, Xiao Ji, Hong-Yan Jing, Fan-Bo |
author_facet | Guo, Qie Sui, Zhong-Guo Xu, Wen Quan, Xiang-Hua Sun, Jia-Lin Li, Xiao Ji, Hong-Yan Jing, Fan-Bo |
author_sort | Guo, Qie |
collection | PubMed |
description | Hepatocellular carcinoma (HCC) is one of the most serious cancers, with rapid progression and high mortality. However, chemotherapy of HCC is hindered by multi-drug resistance (MDR). It is urgent, therefore, to explore new approaches for overcoming MDR of HCC cells. Ubenimex, an inhibitor of CD13, has been used as an immuno-enhancer for treating hematological neoplasms and other solid tumors. Here, we demonstrate that Ubenimex can also reverse MDR in the HCC cell lines HepG2/5-FU and Bel7402/5-FU. Ubenimex inhibits the expression of the proto-oncogene, Pim-3, which is accompanied by decreased expression of BCL-2 and BCL-XL, decreased phosphorylation of Bad, and increased tumor apoptosis. Moreover, Ubenimex decreases expression of the MDR-associated proteins P-gp, MRP3 and MRP2 to enhance intracellular accumulation of Cisplatin, for which down-regulation of Pim-3 is essential. Our results reveal a previously uncharacterized function of Ubenimex in mediating drug resistance in HCC, which suggests that Ubenimex may provide a new strategy to reverse MDR and improve HCC sensitivity to chemotherapeutic drugs via its effects on Pim-3. |
format | Online Article Text |
id | pubmed-5641159 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56411592017-10-24 Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells Guo, Qie Sui, Zhong-Guo Xu, Wen Quan, Xiang-Hua Sun, Jia-Lin Li, Xiao Ji, Hong-Yan Jing, Fan-Bo Oncotarget Research Paper Hepatocellular carcinoma (HCC) is one of the most serious cancers, with rapid progression and high mortality. However, chemotherapy of HCC is hindered by multi-drug resistance (MDR). It is urgent, therefore, to explore new approaches for overcoming MDR of HCC cells. Ubenimex, an inhibitor of CD13, has been used as an immuno-enhancer for treating hematological neoplasms and other solid tumors. Here, we demonstrate that Ubenimex can also reverse MDR in the HCC cell lines HepG2/5-FU and Bel7402/5-FU. Ubenimex inhibits the expression of the proto-oncogene, Pim-3, which is accompanied by decreased expression of BCL-2 and BCL-XL, decreased phosphorylation of Bad, and increased tumor apoptosis. Moreover, Ubenimex decreases expression of the MDR-associated proteins P-gp, MRP3 and MRP2 to enhance intracellular accumulation of Cisplatin, for which down-regulation of Pim-3 is essential. Our results reveal a previously uncharacterized function of Ubenimex in mediating drug resistance in HCC, which suggests that Ubenimex may provide a new strategy to reverse MDR and improve HCC sensitivity to chemotherapeutic drugs via its effects on Pim-3. Impact Journals LLC 2017-08-10 /pmc/articles/PMC5641159/ /pubmed/29069816 http://dx.doi.org/10.18632/oncotarget.20194 Text en Copyright: © 2017 Guo et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Guo, Qie Sui, Zhong-Guo Xu, Wen Quan, Xiang-Hua Sun, Jia-Lin Li, Xiao Ji, Hong-Yan Jing, Fan-Bo Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells |
title | Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells |
title_full | Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells |
title_fullStr | Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells |
title_full_unstemmed | Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells |
title_short | Ubenimex suppresses Pim-3 kinase expression by targeting CD13 to reverse MDR in HCC cells |
title_sort | ubenimex suppresses pim-3 kinase expression by targeting cd13 to reverse mdr in hcc cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641159/ https://www.ncbi.nlm.nih.gov/pubmed/29069816 http://dx.doi.org/10.18632/oncotarget.20194 |
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