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An isocorydine derivative (d-ICD) inhibits drug resistance by downregulating IGF2BP3 expression in hepatocellular carcinoma

In our previous studies, we reported that CD133(+) cancer stem cells (CSCs) were chemoresistant in hepatocellular carcinoma (HCC) and that isocorydine treatment decreased the percentage of CD133(+) CSCs. Here, we found that a derivative of isocorydine (d-ICD) inhibited HCC cell growth, particularly...

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Autores principales: Li, Meng, Zhang, Lixing, Ge, Chao, Chen, Lijuan, Fang, Tao, Li, Hong, Tian, Hua, Liu, Junxi, Chen, Taoyang, Jiang, Guoping, Xie, Haiyang, Cui, Ying, Yao, Ming, Li, Jinjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694821/
https://www.ncbi.nlm.nih.gov/pubmed/26327240
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author Li, Meng
Zhang, Lixing
Ge, Chao
Chen, Lijuan
Fang, Tao
Li, Hong
Tian, Hua
Liu, Junxi
Chen, Taoyang
Jiang, Guoping
Xie, Haiyang
Cui, Ying
Yao, Ming
Li, Jinjun
author_facet Li, Meng
Zhang, Lixing
Ge, Chao
Chen, Lijuan
Fang, Tao
Li, Hong
Tian, Hua
Liu, Junxi
Chen, Taoyang
Jiang, Guoping
Xie, Haiyang
Cui, Ying
Yao, Ming
Li, Jinjun
author_sort Li, Meng
collection PubMed
description In our previous studies, we reported that CD133(+) cancer stem cells (CSCs) were chemoresistant in hepatocellular carcinoma (HCC) and that isocorydine treatment decreased the percentage of CD133(+) CSCs. Here, we found that a derivative of isocorydine (d-ICD) inhibited HCC cell growth, particularly among the CD133(+) subpopulation, and rendered HCC cells more sensitive to sorafenib treatment. d-ICD inhibited IGF2BP3 expression in a time-dependent manner, and IGF2BP3 expression negatively correlated with d-ICD-induced growth suppression. IGF2BP3 overexpression enriched the CD133(+) CSC subpopulation in HCC, enhanced tumor sphere formation and suppressed the cytotoxic effects of sorafenib and doxorubicin. The expression of drug resistance-related genes, including ABCB1 and ABCG2, and the CSC marker CD133 expression was increased after IGF2BP3 overexpression. The significance of these observations was underscored by our findings that high IGF2BP3 expression predicted poor survival in a cohort of 236 patients with HCC and positively correlated with ABCG2 and CD133 expression in vivo. These results suggested that the d-ICD may inhibit HCC cells growth by IGF2BP3 decrease and that IGF2BP3 may serve as a therapeutic target for HCC.
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spelling pubmed-46948212016-01-20 An isocorydine derivative (d-ICD) inhibits drug resistance by downregulating IGF2BP3 expression in hepatocellular carcinoma Li, Meng Zhang, Lixing Ge, Chao Chen, Lijuan Fang, Tao Li, Hong Tian, Hua Liu, Junxi Chen, Taoyang Jiang, Guoping Xie, Haiyang Cui, Ying Yao, Ming Li, Jinjun Oncotarget Research Paper In our previous studies, we reported that CD133(+) cancer stem cells (CSCs) were chemoresistant in hepatocellular carcinoma (HCC) and that isocorydine treatment decreased the percentage of CD133(+) CSCs. Here, we found that a derivative of isocorydine (d-ICD) inhibited HCC cell growth, particularly among the CD133(+) subpopulation, and rendered HCC cells more sensitive to sorafenib treatment. d-ICD inhibited IGF2BP3 expression in a time-dependent manner, and IGF2BP3 expression negatively correlated with d-ICD-induced growth suppression. IGF2BP3 overexpression enriched the CD133(+) CSC subpopulation in HCC, enhanced tumor sphere formation and suppressed the cytotoxic effects of sorafenib and doxorubicin. The expression of drug resistance-related genes, including ABCB1 and ABCG2, and the CSC marker CD133 expression was increased after IGF2BP3 overexpression. The significance of these observations was underscored by our findings that high IGF2BP3 expression predicted poor survival in a cohort of 236 patients with HCC and positively correlated with ABCG2 and CD133 expression in vivo. These results suggested that the d-ICD may inhibit HCC cells growth by IGF2BP3 decrease and that IGF2BP3 may serve as a therapeutic target for HCC. Impact Journals LLC 2015-07-10 /pmc/articles/PMC4694821/ /pubmed/26327240 Text en Copyright: © 2015 Li et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Li, Meng
Zhang, Lixing
Ge, Chao
Chen, Lijuan
Fang, Tao
Li, Hong
Tian, Hua
Liu, Junxi
Chen, Taoyang
Jiang, Guoping
Xie, Haiyang
Cui, Ying
Yao, Ming
Li, Jinjun
An isocorydine derivative (d-ICD) inhibits drug resistance by downregulating IGF2BP3 expression in hepatocellular carcinoma
title An isocorydine derivative (d-ICD) inhibits drug resistance by downregulating IGF2BP3 expression in hepatocellular carcinoma
title_full An isocorydine derivative (d-ICD) inhibits drug resistance by downregulating IGF2BP3 expression in hepatocellular carcinoma
title_fullStr An isocorydine derivative (d-ICD) inhibits drug resistance by downregulating IGF2BP3 expression in hepatocellular carcinoma
title_full_unstemmed An isocorydine derivative (d-ICD) inhibits drug resistance by downregulating IGF2BP3 expression in hepatocellular carcinoma
title_short An isocorydine derivative (d-ICD) inhibits drug resistance by downregulating IGF2BP3 expression in hepatocellular carcinoma
title_sort isocorydine derivative (d-icd) inhibits drug resistance by downregulating igf2bp3 expression in hepatocellular carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694821/
https://www.ncbi.nlm.nih.gov/pubmed/26327240
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