Pachymic Acid Suppresses Endometrial Cancer Cell Migration by Inhibiting the NR3C1 / TGF ‐β/Smad Signaling Pathway

ABSTRACT

Pachymic acid exerts antitumor effects against renal cell carcinoma and breast, lung, and pancreatic cancers; however, its specific inhibitory effect on endometrial cancer progression remains unclear. Therefore, in this study, we investigated the antitumor effects of pachymic acid against endometrial cancer using cell counting kit 8, flow cytometry, wound healing, transwell, cycloheximide chase, and western blot assays. Notably, pachymic acid significantly suppressed the viability, proliferation, and migration of endometrial cancer cells. Nuclear receptor subfamily 3 group C member 1 (NR3C1) was identified as its potential target against endometrial cancer. Pachymic acid promoted NR3C1 degradation. However, NR3C1 overexpression reversed the inhibitory effects of pachymic acid on the proliferation and migration of endometrial cancer cells. Furthermore, an association was observed between NR3C1 expression and the transforming growth factor beta (TGF‐β) pathway. NR3C1 knockdown and pachymic acid treatment reduced protein levels of TGF‐β1 and p‐Smad2/3. TGF‐β pathway inhibitor galunisertib reversed the NR3C1 overexpression‐induced increase in endometrial cancer cell migration. Collectively, our findings suggest that pachymic acid suppresses endometrial cancer cell migration by inhibiting the NR3C1/TGF‐β/Smad signaling pathway, highlighting its potential as a therapeutic agent for endometrial cancer.