Hua Yu Xiao Zheng decoction induces ectopic endometrial stromal cell senescence via inhibiting the PI3K/AKT signaling.

BACKGROUND

Our purpose is to explore the influence of Hua Yu Xiao Zheng (HYXZ) decoction on the senescence of ectopic endometrial stromal cells (ESCs) in endometriosis as well as its relevant mechanisms.

METHODS

The proliferation, apoptosis, migration, and invasion of primary ectopic ESCs was assessed utilizing EdU assay, flow cytometry, and transwell assays. Moreover, the effects of HYXZ decoction on oxidative stress were evaluated using DCFH-DA probe and via measuring MDA, GSH, SOD and GPx levels. The function of HYXZ decoction on cell senescence were explored through utilizing SA-β-gal staining and measuring the cumulative population doubling level and the average telomere length. The protein expression was measured using western blotting analysis. Endometriosis in rats was surgically induced, and the efficacy and mechanism of HYXZ decoction were determined in vivo.

RESULTS

HYXZ decoction inhibited the growth, migration, and invasion of ectopic ESCs, but induced oxidative stress and senescence. HYXZ decoction inhibited PI3K/AKT signaling in ectopic ESCs. PI3K-AKT signaling pathway activator (740Y-P) significantly reversed the inhibitory effects of HYXZ decoction on ectopic ESCs. In rats with endometriosis, oral administration of HYXZ decoction inhibited lesion volume alone with the increased oxidative stress and cell senescence, as well as the decreased PI3K/AKT activity.

CONCLUSION

HYXZ decoction might repress the growth and migration of ectopic ESCs, and induce oxidative stress and senescence through suppressing PI3K/AKT signaling. This finding indicates that HYXZ decoction may be a potential therapeutic drug against endometriosis.