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

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.

Inhibitory effects of estetrol on the invasion and migration of immortalized human endometrial stromal cells

“…We previously established a cellular endometriosis model using immortalized human endometrial stromal cells (HESCs). Employing this model we reported recently that the NF-κB inhibitor DHMEQ inhibited MLCK-dependent migration and invasion of HESCs [16]. Tissue and cell movement are involved in the etiology of endometriosis, therefore, cell migration/ invasion were examined in our E4 study.…”