Abstract
Type II endometrial carcinoma typically exhibits aggressive metastasis and results in a poor prognosis. Siegesbeckia orientalis Linne is a traditional Chinese medicinal herb with several medicinal benefits, including the cytotoxicity against various cancers. This study investigates the inhibitory effects of S. orientalis ethanol extract (SOE) on the migration and invasion of endometrial cancer cells, which were stimulated by transforming growth factor β (TGFβ). The inhibitory effects were evaluated by determining wound healing and performing the Boyden chamber assay. This study reveals that SOE can inhibit TGFβ1-induced cell wound healing, cell migration, and cell invasion in a dose-dependent manner in RL95-2 and HEC-1A endometrial cancer cells. SOE also reversed the TGFβ1-induced epithelial-mesenchymal transition, including the loss of the cell-cell junction and the lamellipodia-like structures. Western blot analysis revealed that SOE inhibited the phosphorylation of ERK1/2, JNK1/2, and Akt, as well as the expression of MMP-9, MMP-2, and u-PA in RL95-2 cells dose-dependently. The results of this investigation suggest that SOE is a potential anti-metastatic agent against human endometrial tumors.
Highlights
Endometrial cancer is a common gynecologic malignancy in the Western world [1,2]
We have demonstrated that S. orientalis ethanol extract (SOE) inhibits the growth of RL95-2 human endometrial cancer cells in a dose-dependent manner, and this effect is associated with G2/M phase cell cycle arrest, activation of caspase-3, -8, and -9, upregulation of Bad, Bak, and Bax, and downregulation of Bcl-2 and
The present study investigates the inhibitory effects of SOE on the motility and invasion of endometrial cancer cells under the stimulation by TGFβ1
Summary
Endometrial cancer is a common gynecologic malignancy in the Western world [1,2]. Endometrial cancer can be classified into Type I and Type II based on clinical behavior and morphological phenotype. Type I cases are low-stage and low-grade, while. Type II cases are advanced-stage and aggressive [4]. Most cases of Type I can be diagnosed at an early stage because some symptoms would appear in this stage, and such cases present a high survival percentage following primary surgery. Type II patients typically have a poor prognosis because the carcinoma has an aggressive phenotype that is characterized by lymphovascular invasion, high histological grade, and myometrial invasion, resulting in distant metastases via the hematogenous route [5]
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