Oncotarget

Research Papers:

Radioimmunotherapy for CD133(+) colonic cancer stem cells inhibits tumor development in nude mice

Weng Dinghu, Jin Xueyan, Qin Saimei, Lan Xiaoli, Chen Chong, Sun Xun, She Xianliang, Dong Changling and An Rui _

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Oncotarget. 2017; 8:44004-44014. https://doi.org/10.18632/oncotarget.16868

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Abstract

Weng Dinghu1,2, Jin Xueyan1,2, Qin Saimei1,2, Lan Xiaoli1,2, Chen Chong1,2, Sun Xun1,2, She Xianliang1,2, Dong Changling3 and An Rui1,2

1Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

2Hubei Key Laboratory of Molecular Imaging, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

3Department of Neurosurgery, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, China

Correspondence to:

An Rui, email: [email protected]

Keywords: radioimmunotherapy, cancer stem cells, CD133, iodine-131, N-succinimidyl 3- (tri-n-butylstannyl) benzoate

Received: October 11, 2016     Accepted: March 14, 2017     Published: April 06, 2017

ABSTRACT

Accumulating evidence indicates that cancer stem cells (CSCs) are the cause of tumor drug/radio-resistance or distant metastasis; therefore, it is essential to eliminate CSCs to cure cancer completely. The purpose of this study was to utilize radioimmunotherapy (RIT) to target CD133(+) colonic CSCs and observe whether this prevented tumor development, by assessing the maximum tolerated dose (MTD) of HCT116 tumor-bearing nude mice with escalating doses of 131I-AC133.1 monoclonal antibody (mAb), and determining the therapeutic efficacy of RIT with 131I-AC133.1 mAb. For RIT trials, animals were randomly divided into 4 groups of 6 per group, and injected with 131I-AC133.1 mAb (16.65 MBq/100 μl), AC133.1 mAb (173.1 μg/100 μl), saline (100 μl), or unrelated IgG1 as an isotype control. Iodine-131 was radiolabeled to AC133.1 mAb by conjugation with N-succinimidyl 3-(tri-n-butylstannyl) benzoate. The MTD of HCT116 tumor-bearing nude mice was 16.65 MBq. Both of the tumor volume doubling time and the survival time of the 131I-AC133.1 mAb group were significant longer than other groups (P < 0.001). CD133 expression was assessed by flow cytometry. Protein levels of cancer stem-like biomarkers (CD133, ALDH1, Lgr5, Vimentin, Snail1), and the proliferative rate of 131I-AC133.1 mAb group were lower than other groups (P<0.001); while its protein level of E-cadherin was higher than other groups. Furthermore, a large proportion of tumor necrosis was also observed in the 131I-AC133.1 mAb group, suggesting that RIT can destroy CSCs and effectively inhibit tumor development.


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