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

被引:40
|
作者
Li, Meng [1 ,2 ]
Zhang, Lixing [2 ]
Ge, Chao [2 ]
Chen, Lijuan [1 ,2 ]
Fang, Tao [2 ]
Li, Hong [2 ]
Tian, Hua [2 ]
Liu, Junxi [3 ,4 ]
Chen, Taoyang [5 ]
Jiang, Guoping [6 ]
Xie, Haiyang [6 ]
Cui, Ying [7 ]
Yao, Ming [2 ]
Li, Jinjun [2 ]
机构
[1] Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Shanghai 200433, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Canc Inst, State Key Lab Oncogenes & Related Genes, Renji Hosp,Sch Med, Shanghai 200030, Peoples R China
[3] Chinese Acad Sci, Lanzhou Inst Chem Phys, Key Lab Chem Northwestern Plant Resources, Lanzhou 730000, Peoples R China
[4] Chinese Acad Sci, Lanzhou Inst Chem Phys, Key Lab Fornatural Med Gansu Prov, Lanzhou 730000, Peoples R China
[5] Qi Dong Peoples Hosp, Qi Dong Liver Canc Inst, Qi Dong, Jiangsu, Peoples R China
[6] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Gen Surg, Hangzhou 310003, Zhejiang, Peoples R China
[7] Guangxi Med Univ, Canc Inst Guangxi, Nanning, Peoples R China
基金
中国国家自然科学基金;
关键词
isocorydine; IGF2BP3; cancer stem cell; CD133; hepatocellular carcinoma; MESSENGER-RNA; SIDE-POPULATION; LIQUID-CHROMATOGRAPHY; MULTIDRUG-RESISTANCE; EFFLUX PUMP; RAT PLASMA; STEM-CELLS; CANCER; PROGNOSIS; CHEMORESISTANCE;
D O I
10.18632/oncotarget.4438
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:25149 / 25160
页数:12
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