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The Clinical and Experimental Research on the Treatment of Endometriosis with Thiostrepton NEWS RELEASE: 04-04-2018

The article by Jian V. Zhang and colleagues is published in Anti-Cancer Agents in Medicinal Chemistry, Volume 19, Issue 3, 2019

Forkhead Box M1 (FOXM1), which known as Trident, HNF-3, HFH-11, MPP2, and Win, is a transcriptional factor that plays an important role in cell proliferation, differentiation, and transformation. As one of the early up-regulated proteins in cancerogenesis, FOXM1 is frequently activated in tumors. This research studied the expression and the possible mechanism of FOXM1 and evaluated the effects of thiostrepton in an endometriotic rat model.

The research concluded two part. On the one hand, we constructed the rats model of endometriosis. Observed the expression of FOXM1 in endometriosis tissues. Explored the possible mechanism of FOXM1 action, like EKR?FOXM1 and MMP9 Signaling Pathway. Fifty female Wistar rats were surgically induced with endometriosis. After 4 weeks of observation, twenty and thirty rats were randomly allocated to an ovariectomized (OVX) group and a treatment group, respectively. The OVX group was ovariectomized and randomly divided into an OVX-estrogen group and a control (OVX -oil) group. All rats were allowed a resting period of 3 days prior to any operation. The rats in the estrogen group were given estradiol (20 μg/kg, 0.1 ml /d), while the control group was treated with an equivalent amount of sesame oil. Every group was injected with subcutaneous injection for 7 days. Our results showed that FOXM1 is enrich in nucleus of an ectopic endometrium when compared with an eutopic uterus. Furthermore, we found that an ERK/FOXM1/matrix metalloproteinase-9 (MMP9) signaling pathway might result in the establishment and development of endometriosis.

On the other hand, thiostrepton is a small-molecule inhibitor of the transcription factor FOXM1. We evaluated the effects of thiostrepton in an endometriotic rat model. The treatment group was randomly divided into three groups to receive the following: TST at 150 mg/kg, ip.; TST at 250 mg/kg, ip.; or sterile normal saline, ip. The groups received these dosages every 2 days for 2 weeks. Lesion growth, histological examination, and protein expression were subsequently analyzed using caliper measurement, histology, immunostaining, and Western blot after each rat received an injection in its own group. Our results showed that a thiostrepton concentration dependently reduced the expression of FOXM1, MMP9 and Bcl-2 in endometriotic lesions of the treated rats. Statistical significance was accepted for a value of P < 0.05.

In conclusion, we postulate that thiostrepton could inhibit the endometriotic lesions, at least in part, by decreasing the FOXM1 expression and exerting a pro-apoptotic effect. We reported for the first time that FOXM1 expresses in experimental endometriosis rat and thiostrepton may also be suitable for the administration of endometriosis by inhibiting the growth of endometriotic implants.

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