Canagliflozin Alleviates Progestin Resistance by Suppressing RARβ/CRABP2 Signaling in THRB Knockout Endometrial Cancer Cells

    April 2025 in “ Frontiers in Pharmacology
    Ye Yang, Jieyun Zhou, Qiaoying Lv, Qicheng Ni, Baichun Hu, Yulong Wang, Suqing Qu, Guoting Li, Wenjie Yang, Ruihua Zhong, Xiaojun Chen, Yan Zhu
    TLDR Canagliflozin helps overcome progestin resistance in certain endometrial cancer cells.
    The study explores the potential of Canagliflozin (CANA) to overcome progestin resistance in endometrial cancer cells lacking thyroid hormone receptor beta (THRB). It demonstrates that CANA effectively suppresses the RARβ/CRABP2 signaling pathway, which is associated with progestin resistance. CANA, alone or combined with medroxyprogesterone acetate (MPA), significantly inhibits tumor growth and promotes apoptosis in both in vitro and in vivo models. The findings suggest that CANA could be a promising therapeutic agent for treating progestin-resistant endometrial cancer, although further clinical validation is necessary due to the study's limitations, including a small sample size.
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