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

Oncotarget
Meng LiJinjun Li

Abstract

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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Citations

Apr 20, 2018·Phytotherapy Research : PTR·Bahare SalehiJavad Sharifi-Rad
Dec 25, 2019·Natural Product Research·Juan QinYao-Lan Li
Feb 6, 2020·Frontiers in Cell and Developmental Biology·Caterina Mancarella, Katia Scotlandi
Sep 23, 2020·International Journal of Molecular Sciences·Jonas WeißeTony Gutschner
Dec 24, 2017·Journal of Molecular Endocrinology·Caterina Mancarella, Katia Scotlandi
Apr 29, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Caterina MancarellaKatia Scotlandi
Apr 14, 2020·Current Pharmaceutical Design·Peng-Fei WangShu-Lin Liu
Jul 27, 2021·Current Therapeutic Research, Clinical and Experimental·Lei SongJunxi Liu
Apr 14, 2021·Current Drug Targets·Maria Manuela EstevinhoJoão Carvalho

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Methods Mentioned

BETA
PCR
transfection
flow cytometry
ELISA

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