Research Papers:

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

Meng Li, Lixing Zhang, Chao Ge, Lijuan Chen, Tao Fang, Hong Li, Hua Tian, Junxi Liu, Taoyang Chen, Guoping Jiang, Haiyang Xie, Ying Cui, Ming Yao and Jinjun Li _

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Oncotarget. 2015; 6:25149-25160. https://doi.org/10.18632/oncotarget.4438

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Meng Li1,2,*, Lixing Zhang2,*, Chao Ge2, Lijuan Chen1,2, Tao Fang2, Hong Li2, Hua Tian2, Junxi Liu3, Taoyang Chen4, Guoping Jiang5, Haiyang Xie5, Ying Cui6, Ming Yao2, Jinjun Li2

1School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai, China

2State Key Laboratrory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

3Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory Fornatural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, China

4Qi Dong Liver Cancer Institute, Qi Dong People's Hospital, Qi Dong, Jiangsu Province, China

5Department of General Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

6Cancer Institute of Guangxi, Guangxi Medical University, Nanning, China

*These authors have contributed equally to this work

Correspondence to:

Jinjun Li, e-mail: [email protected]

Keywords: isocorydine, IGF2BP3, cancer stem cell, CD133, hepatocellular carcinoma

Received: April 04, 2015     Accepted: June 29, 2015     Published: July 10, 2015


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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