Background: Dysregulated migration and invasion of endometrial stromal cells is
implicated in the pathogenesis of endometriosis. Hypoxia functions as critical
microenvironmental factor that results in promotion of endometrial stromal cells
migration and invasion through up-regulation of autophagy. Paeonol functioned as
a tumor suppressor in human ovarian cancer and promoted cytoprotective autophagy.
However, the role of paeonol in hypoxia-induced autophagy in endometriosis
remains unknown. Methods: Stromal cells were isolated from endometriotic patients by enzymatic
digestion of ectopic endometrial tissues, and then characterized by
immunohistochemical analysis of cytoskeleton 19 (CK19) and vimentin. Cellular
morphology was evaluated under microscope. Cell viability, proliferation and
apoptosis of stromal cells were assessed by Cell Counting Kit-8, EdU labeling and
flow cytometry, respectively. Wound healing and transwell assays were performed
to detect metastasis of the stromal cells. Hypoxia-induced autophagy was
evaluated through immunohistochemistry and western blot. Results: Paeonol treatment dosage dependently decreased cell proliferation and
metastasis of the ectopic endometrial stromal cells (ecESCs), while promoted the
cell apoptosis. Hypoxia-induced autophagy in the ecESCs was repressed by paeonol
through down-regulation of LC3-II/LC3-I and Beclin-1, while up-regulation of p62.
Hypoxia-inducible factor-1
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Original Research
Paeonol alleviates migration and invasion of endometrial stromal cells by reducing HIF-1-regulated autophagy in endometriosis
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1
Center of Reproduction and Genetics Integrated Traditional Chinese and Western Medicine, The Hospital Affiliated to Shandong University of Traditional Chinese Medicine, 250014 Jinan, Shandong, China
2
Department of Gynecology of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, 250014 Jinan, Shandong, China
*Correspondence: qiyinghuaok@126.com (Yinghua Qi)
Front. Biosci. (Landmark Ed) 2021, 26(9), 485–495;
https://doi.org/10.52586/4961
Submitted: 16 March 2021 | Revised: 28 June 2021 | Accepted: 11 August 2021 | Published: 30 September 2021
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Abstract
Keywords
Paeonol
Metastasis
Endometrial stromal cells
HIF-1α
Autophagy
Endometriosis
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