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Development of a novel insulin receptor (IR) antagonist that exhibits anti-breast tumor activity

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Abstract

Many reports have indicated that the insulin receptor (IR) causes tumorigenesis and the development of breast cancer. It has been considered a potential target for treating IR-related tumors. Traditionally, there are two categories of insulin receptor (IR) antagonists, they are small molecule antagonists and anti-IR antibodies. Here, we describe a new method (anti-idiotypic antibody strategy) for the development of IR antagonist. Hybridoma technology was employed to design and identify a series of anti-idiotypic antibodies against insulin. After repeated screening and identification, an anti-idiotypic antibody against IR (AK98) was obtained. Analysis through competitive ELISA and competitive receptor binding indicated that AK98 mimicked the receptor binding epitope of insulin. The interaction between AK98 and IR was determined using indirect immunofluorescence, immunoelectron microscopy, and Immunoprecipitation-Western (IP-WB). Further research using a tumor cell model revealed that AK98 inhibited insulin-IR binding and IR-mediated intracellular signaling pathways. Conclusively, the main purpose of this paper is that we proposed a new method (anti-idiotypic antibody strategy) to develop the insulin receptor (IR) antagonist (AK98), and a series of experiments showed that the anti-idiotypic antibody (AK98) exhibited good antagonistic activity against IR. This work suggests that the anti-idiotypic antibody may be a potential strategy to develop IR antagonists that can be used in treating breast cancer.

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Abbreviations

IR:

Insulin receptor

IGFR:

Insulin-like growth factor

AKT:

Protein kinase B

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Acknowledgements

This work were supported by Shenzhen Science and Technology plan project (no. JCYJ20160428135756806), (no. JCYJ20160428141830465); National Natural Science Foundation of China (no. 81601382); Guangdong basic and Applied Basic Research Foundation (2020A1515010179).

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Authors and Affiliations

  1. Department of Laboratory, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong, People’s Republic of China

    Kuang Wenbin, Deng Qiuchan & He Dabao

  2. Department of Neurosurgery, The Second People’s Hospital of Lianyungang, Jiangsu, 222000, People’s Republic of China

    Liu Xiaoqin

  3. Department of Thyroid and Breast Surgery, The Second People’s Hospital of Lianyungang, Jiangsu, 222000, People’s Republic of China

    Zheng Xinwen, Shen Fangyuan & Zhu Shuangjiu

  4. Department of Pathology, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong, People’s Republic of China

    Xiao Xiaoqin

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  1. Kuang Wenbin
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  2. Liu Xiaoqin
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  3. Deng Qiuchan
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  4. Zheng Xinwen
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  5. Xiao Xiaoqin
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  6. Shen Fangyuan
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  7. He Dabao
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  8. Zhu Shuangjiu
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Contributions

KWB, LXQ, DQC and ZXW: performed the experiments; KWB: drafted the manuscript; SFY and HDB: edited the manuscript; ZSJ: conceived of the study, and participated in its design and coordination.

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Correspondence to Zhu Shuangjiu.

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Wenbin, K., Xiaoqin, L., Qiuchan, D. et al. Development of a novel insulin receptor (IR) antagonist that exhibits anti-breast tumor activity. Human Cell 33, 1204–1217 (2020). https://doi.org/10.1007/s13577-020-00381-3

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  • DOI: https://doi.org/10.1007/s13577-020-00381-3

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