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. 2021 Sep 8;11:682917. doi: 10.3389/fonc.2021.682917

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Copyright © 2021 Liu, Zhang, Xu, Liu, Sun, Che and He

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The mechanism of apigenin for inhibiting the proliferation of ovarian cancer cells. After histamine binds to its receptors, it up-regulates the expression of ERα and down-regulates the expression ERβ (blue line). ERs binds to the estrogen response element (ERE) sequence of the target gene promoter after dimerization (38), activating the transcription of downstream target gene (40, 41), such as cell cycle regulators (CCND1, c-Myc) and apoptosis-related proteins (BCL2, BCLXL), etc., which works on promoting cell proliferation and tumor development. Apigenin suppresses PI3K/AKT/mTOR signaling pathway by regulating the expression level of ERα/ERβ (red line), thereby attenuates the development of ovarian cancer induced by histamine.