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

作者：Chen Sun, Pan Liu, Lijian Pei, Mengyun Zhao, Yuguang Huang · 发表于：Frontiers in Oncology · 年份：2022 · DOI：10.3389/fonc.2022.837974 · 被引用次数：40 · 研究领域：Cancer, Stress, Anesthesia, and Immune Response、Ferroptosis and cancer prognosis、Cancer Research and Treatment

Background Triple-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. Methods We 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 Fe 2+ levels, and the expression and localization of ferroptosis-related proteins were investigated. Results We 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 Fe 2+ assay, western blotting, and multiplex immunohistochemistry revealed that propofol not only induced apoptosis but also triggered ferroptosis-related changes, including morphological changes of mitochond...