Inhibition of MLCK‑mediated migration and invasion in human endometriosis stromal cells by NF‑κB inhibitor DHMEQ

Lin,Yinzhi; Kojima,Shiori; Ishikawa,Ayaka; Matsushita,Hiroshi; Takeuchi,Yuka; Mori,Yuki; Ma,Jun; Takeuchi,Kosei; Umezawa,Kazuo; Wakatsuki,Akihiko

doi:10.3892/mmr.2023.13028

Inhibition of MLCK‑mediated migration and invasion in human endometriosis stromal cells by NF‑κB inhibitor DHMEQ

Authors:
- Yinzhi Lin
- Shiori Kojima
- Ayaka Ishikawa
- Hiroshi Matsushita
- Yuka Takeuchi
- Yuki Mori
- Jun Ma
- Kosei Takeuchi
- Kazuo Umezawa
- Akihiko Wakatsuki
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Affiliations: Department of Molecular Target Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan, Department of Obstetrics and Gynecology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan, Department of Biology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan
Published online on: June 9, 2023 https://doi.org/10.3892/mmr.2023.13028
Article Number: 141
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endometriosis is initiated by the movement of endometrial cells in the uterus to the fallopian tubes, the ovaries and the peritoneal cavity after the shedding of the uterus lining. To cause endometriosis, it is often necessary for these endometrial cells to migrate, invade and grow at the secondary site. In the present study, immortalized human endometriosis stromal cells (HESC) were employed to look for the inhibitors of migration and invasion. Using a chemical library of bioactive metabolites, it was found that an NF‑κB inhibitor, DHMEQ, inhibited the migration and invasion of HESC. Both whole‑genome array and metastasis PCR array analyses suggested the involvement of myosin light chain kinase (MLCK) in the mechanism of inhibition. DHMEQ was confirmed to inhibit the expression of MLCK and small inhibitory RNA knockdown of MLCK reduced cellular migration and invasion. The addition of DHMEQ to the knockdown cells did not further inhibit migration and invasion. DHMEQ is particularly effective in suppressing disease models by intraperitoneal (IP) administration and this therapy is being developed for the treatment of inflammation and cancer. DHMEQ IP therapy may also be useful for the treatment of endometriosis.

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