PT  - JOURNAL ARTICLE
AU  - Wang, Qin
AU  - Liu, Xueting
AU  - Li, Bingwei
AU  - Yang, Xiaojie
AU  - Lu, Wenbao
AU  - Li, Ailing
AU  - Li, Hongwei
AU  - Zhang, Xiaoyan
AU  - Han, Jianqun
TI  - <strong><strong>Sodium pentobarbital</strong><strong> suppresses breast cancer cells</strong><strong> growth partly via normalizing microcirculatory hemodynamics and oxygenation in tumors</strong></strong>
AID  - 10.1124/jpet.121.001058
DP  - 2022 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - JPET-AR-2021-001058
4099  - http://jpet.aspetjournals.org/content/early/2022/05/05/jpet.121.001058.short
4100  - http://jpet.aspetjournals.org/content/early/2022/05/05/jpet.121.001058.full
AB  - Breast cancer remains the leading cause of cancer-related death among women worldwidely. Sodium pentobarbital was found to play an inhibitory role in glioma growth in rats. In this study, we aim to evaluate the effects of sodium pentobarbital on breast cancer growth both in vitro and in vivo, and its impacts on the microcirculatory changes both on skin and tumor surface in mice bearing subcutaneous xenograft. Cell counting assay was used to assess the anti-proliferative 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 (THb, µM), and red blood cell (RBC) tissue fraction (%) were examined simultaneously by using EPOS 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 in 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.