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Mechanism of Hirudin-Mediated Inhibition of Proliferation in Ovarian Cancer Cells

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Abstract

To investigate the inhibitory effect of hirudin on the cell proliferation of human ovarian cancer A2780 cells by preventing thrombin and its underlying molecular mechanism. Cell Counting Kit-8 (CCK-8) method was used to detect the effect of different concentrations of hirudin and thrombin on the cell proliferation of A2780 cells. PAR-1 wild-type overexpression plasmid was constructed utilizing enzyme digestion identification, and it was transferred to A2780 cells. Sequencing and Western blot were used to detect the changes in PAR-1 protein expression. Western blot detection of PKCα protein phosphorylation in A2780 cells was performed. We also implemented quantitative PCR to detect the mRNA expression levels of epithelial-mesenchymal transition (EMT)-related genes, CDH2, Snail, and Vimentin, in A2780 cells. 1 μg/ml hirudin treatment maximally inhibited the promotion of A2780 cell proliferation by thrombin. Hirudin inhibited the binding of thrombin to the N-terminus of PAR-1, hindered PKCα protein phosphorylation in A2780 cells, and downregulated the mRNA expression levels of CDH2, Snail, and Vimentin. In conclusion, hirudin inhibits the cell proliferation of ovarian cancer A2780 cells, and the underlying mechanism may be through downregulating the transcription level of EMT genes, CDH2, Snail, and Vimentin. This study indicates that hirudin may have a therapeutic potential as an anti-cancer agent for ovarian cancer.

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All data generated or used during the study appear in the submitted article.

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Funding

This work was supported by the Traditional Chinese Medicine Science and Technology Program Project of Zhejiang Province (No. 2022ZA140).

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Authors and Affiliations

  1. Oncology Department of Integrated Traditional Chinese and Western Medicine, Hangzhou Cancer Hospital, No. 34 Yanguan Lane, Ziyang Street, Shangcheng District, Hangzhou, 310000, Zhejiang Province, China

    Junyan Kou, Liwei Ni & Tingting Shao

  2. Department of Oncology & Hematology, Hangzhou Red Cross Hospital, Hangzhou, 310003, Zhejiang Province, China

    Liujie Gao & Jiyuan Ding

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  1. Junyan Kou
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Contributions

JK and JD dedicated to the study concepts, study design and responsible for the integrity of the entire study; LG and LN were involved in the data acquisition, data analysis and statistical analysis; TS carried out the literature research and manuscript preparation and manuscript writing. All authors have reviewed and approved this article.

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Correspondence to Jiyuan Ding.

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The current study was conducted with the approval of the Ethical Committees of Hangzhou Cancer Hospital.

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Kou, J., Gao, L., Ni, L. et al. Mechanism of Hirudin-Mediated Inhibition of Proliferation in Ovarian Cancer Cells. Mol Biotechnol 66, 1062–1070 (2024). https://doi.org/10.1007/s12033-023-01003-7

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  • DOI: https://doi.org/10.1007/s12033-023-01003-7

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