Propofol Inhibits Proliferation and Augments the Anti-Tumor Effect of Doxorubicin and Paclitaxel Partly Through Promoting Ferroptosis in Triple-Negative Breast Cancer Cells

Frontiers in Oncology

Pan Liu²  Mengyun Zhao⁴  Chen Sun⁴  Yuguang Huang⁴  Lijian Pei⁵ 

[1] Department of Anesthesiology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China;Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China;Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China;Joint Laboratory of Anesthesia and Pain, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China;Outcomes Research Consortium, Cleveland, OH, United States;

关键词: propofol;    triple-negative breast cancer;    ferroptosis;    propofol injectable emulsion;    fospropofol disodium;   

DOI  :  10.3389/fonc.2022.837974

来源: DOAJ

【 摘 要 】

BackgroundTriple-negative breast cancer (TNBC) is relatively common in women and is associated with a poor prognosis after surgery and adjuvant chemotherapy. Currently, the mechanism underlying the relationship between propofol and breast cancer is controversial and limited to cell apoptosis. Moreover, there are only a few studies on the effect of propofol on the chemotherapeutic sensitivity of TNBC cells. Therefore, this study explored whether propofol and its commonly used clinical formulations affect the proliferation and chemotherapeutic effects on TNBC cells by regulating cell ferroptosis.MethodsWe selected MDA-MB-231 cells, and the effects of propofol, propofol injectable emulsion (PIE), or fospropofol disodium, alone or combined with doxorubicin or paclitaxel on cell viability, apoptosis, intracellular reactive oxygen species (ROS) accumulation, ferroptosis-related morphological changes, intracellular Fe2+ levels, and the expression and localization of ferroptosis-related proteins were investigated.ResultsWe found that propofol significantly inhibited MDA-MB-231 cell proliferation, and all three propofol formulations augmented the anti-tumor effects of doxorubicin and paclitaxel. The results from the ROS assay, transmission electron microscopy, intracellular Fe2+ assay, western blotting, and multiplex immunohistochemistry revealed that propofol not only induced apoptosis but also triggered ferroptosis-related changes, including morphological changes of mitochondria, increased intracellular ROS levels, and intracellular iron accumulation in MDA-MB-231 cells. The ferroptosis-related p53-SLC7A11-GPX4 pathway was also altered under different treatment propofol, doxorubicin, or paclitaxel regimens.ConclusionPropofol showed anti-proliferation effects on TNBC cells and could be a potential adjuvant to enhance the chemotherapeutic sensitivity of TNBC cells partly by promoting cell ferroptosis.

【 授权许可】

Unknown