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

NF-κB 抑制剂 DHMEQ 抑制 MLCK 介导的人类子宫内膜异位症基质细胞迁移和侵袭

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

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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