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Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Sodium Pentobarbital Suppresses Breast Cancer Cell Growth Partly via Normalizing Microcirculatory Hemodynamics and Oxygenation in Tumors

Qin Wang, Xueting Liu, Bingwei Li, Xiaojie Yang, Wenbao Lu, Ailing Li, Hongwei Li, Xiaoyan Zhang and Jianqun Han
Journal of Pharmacology and Experimental Therapeutics July 2022, 382 (1) 11-20; DOI: https://doi.org/10.1124/jpet.121.001058
Qin Wang
Microhemodynamics Laboratory, Institute of Microcirculation (Q.W., X.Y., H.Q.),
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Xueting Liu
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Bingwei Li
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Xiaojie Yang
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Wenbao Lu
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Ailing Li
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Hongwei Li
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Xiaoyan Zhang
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Jianqun Han
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Abstract

Breast cancer remains the leading cause of cancer-related death among women worldwide. Sodium pentobarbital was found to play an inhibitory role in glioma growth in rats. In this study, we aimed to evaluate the effects of sodium pentobarbital on breast cancer growth both in vitro and in vivo, and its impacts on the microcirculatory changes on both skin and tumor surface in mice bearing subcutaneous xenograft. Cell counting assay was used to assess the antiproliferative effect of sodium pentobarbital on MDA-MB-231 breast cancer cells. Subcutaneous xenograft model was established to study the role of sodium pentobarbital on in vivo tumor growth. Speed-resolved blood perfusion, hemoglobin oxygen saturation (SO2, %), total hemoglobin tissue concentration (ctTHb, μM), and red blood cell (RBC) tissue fraction (%) were examined simultaneously by using enhanced perfusion and oxygen saturation system to investigate the effects of sodium pentobarbital on microcirculatory hemodynamics and oxygenation. Sodium pentobarbital suppressed breast tumor growth both in vitro and in vivo. Cutaneous blood flux in nutritive capillaries with low-speed flow was significantly increased in tumor-bearing mice, and high-dose sodium pentobarbital treatment cause a reduction in this low-speed blood flux, whereas sodium pentobarbital therapy caused an elevated blood flux in larger microvessels with mid and high speed in a dose-dependent manner. Different doses of sodium pentobarbital exerted different actions on SO2, ctTHb, and RBC tissue fraction. Collectively, the inhibitory effect of sodium pentobarbital on breast tumor growth was at least partly associated with its ability to normalize microcirculatory hemodynamics and oxygenation in tumors.

SIGNIFICANCE STATEMENT This study is the first to demonstrate the inhibiting effect of sodium pentobarbital on breast cancer growth both in vitro and in vivo, and such an inhibition was at least partly associated with its ability to normalize microcirculatory hemodynamics and oxygenation in tumors.

Footnotes

    • Received December 17, 2021.
    • Accepted April 26, 2022.
  • ↵1 Q.W. and X.L. contributed equally to this work

  • This research was funded by the Institute of Microcirculation, Peking Union Medical College Fundamental Research Fund [Grant/Award WXH2020-02].

  • The authors declare no conflict of interest.

  • https://doi.org/10.1124/jpet.121.001058.

  • Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 382 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 382, Issue 1
1 Jul 2022
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Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Sodium Pentobarbital Suppresses Breast Cancer

Qin Wang, Xueting Liu, Bingwei Li, Xiaojie Yang, Wenbao Lu, Ailing Li, Hongwei Li, Xiaoyan Zhang and Jianqun Han
Journal of Pharmacology and Experimental Therapeutics July 1, 2022, 382 (1) 11-20; DOI: https://doi.org/10.1124/jpet.121.001058

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Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Sodium Pentobarbital Suppresses Breast Cancer

Qin Wang, Xueting Liu, Bingwei Li, Xiaojie Yang, Wenbao Lu, Ailing Li, Hongwei Li, Xiaoyan Zhang and Jianqun Han
Journal of Pharmacology and Experimental Therapeutics July 1, 2022, 382 (1) 11-20; DOI: https://doi.org/10.1124/jpet.121.001058
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