Proteomics Analysis Revealed Smad3 as a Potential Target of the Synergistic Antitumor Activity of Disulfiram and Cisplatin in Ovarian Cancer

  • Авторы: Du R.1, Sun F.2, Li K.3, Qi J.4, Zhong W.5, Wang W.6, Sun Q.4, Deng Q.4, Wang H.7, Nie J.2, Ding C.3, Hong B.8
  • Учреждения:
    1. School of Basic Medical Science, Anhui Medical University
    2. Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science,, Chinese Academy of Sciences
    3. State Key Laboratory of Genetic Engineering, Human Phenome Institute, Institutes of Biomedical Sciences, School of Life Sciences, Zhongshan Hospital, Fudan University
    4. Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences
    5. Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China
    6. Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine,, University of Science and Technology of China
    7. Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science,, Chinese Academy of Sciences,
    8. School of Basic Medical Science,, Anhui Medical University
  • Выпуск: Том 23, № 15 (2023)
  • Страницы: 1754-1764
  • Раздел: Oncology
  • URL: https://kld-journal.fedlab.ru/1871-5206/article/view/694348
  • DOI: https://doi.org/10.2174/1871520623666230516161200
  • ID: 694348

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Аннотация

Introduction:Among gynecological cancers, ovarian cancer has a high mortality rate. Cisplatin-based chemotherapy is commonly used for the treatment of ovarian cancer. However, the clinical efficacy of cisplatin in ovarian cancer is limited due to the development of chemo-resistance during treatment.

Objective: In the study, we aimed to investigate the synergistic anti-cancer activity and targets of the FDA-approved drug disulfiram combined with cisplatin in ovarian cancer.

Methods: The cell viability was determined by Celltier-Glo luminescent assay. The synergistic anti-cancer activity was assessed by combination index. Cell cycle and apoptosis were detected by flow cytometry. The in vivo anti-tumor activity and side effects were evaluated using a xenografted mice model. The synergistic anti-cancer targets were identified by a mass spectrometry-based proteomics analysis.

Results: In this study, we first found that disulfiram synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant ovarian cancer cells, which was accompanied by the enhanced induction of cellular apoptosis. Secondly, the in vivo study demonstrated that the combination treatment of disulfiram and cisplatin dramatically inhibited tumor growth and had no apparent side effects in ovarian cancer xenografted mice. Finally, proteomics analysis identified SMAD3 as a potential target of disulfiram-cisplatin combined treatment, and the down-regulation of SMAD3 could increase cisplatin-induced cell death in ovarian cancer.

Conclusion: Combination treatment of disulfiram and cisplatin synergistically inhibited the growth of ovarian cancer through down-regulating SMAD3. As a repurposed drug, disulfiram could be quickly transformed into a clinic to overcome cisplatin resistance for the treatment of ovarian cancer.

Об авторах

Ruiping Du

School of Basic Medical Science, Anhui Medical University

Email: info@benthamscience.net

Feilong Sun

Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science,, Chinese Academy of Sciences

Email: info@benthamscience.net

Kai Li

State Key Laboratory of Genetic Engineering, Human Phenome Institute, Institutes of Biomedical Sciences, School of Life Sciences, Zhongshan Hospital, Fudan University

Email: info@benthamscience.net

Jian Qi

Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences

Email: info@benthamscience.net

Wen Zhong

Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China

Email: info@benthamscience.net

Wei Wang

Department of Pathology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine,, University of Science and Technology of China

Email: info@benthamscience.net

Qiuyan Sun

Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences

Email: info@benthamscience.net

Qingmei Deng

Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences

Email: info@benthamscience.net

Hongzhi Wang

Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science,, Chinese Academy of Sciences,

Email: info@benthamscience.net

Jinfu Nie

Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science,, Chinese Academy of Sciences

Email: info@benthamscience.net

Chen Ding

State Key Laboratory of Genetic Engineering, Human Phenome Institute, Institutes of Biomedical Sciences, School of Life Sciences, Zhongshan Hospital, Fudan University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Bo Hong

School of Basic Medical Science,, Anhui Medical University

Автор, ответственный за переписку.
Email: info@benthamscience.net

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