TY - JOUR
T1 - Isoliquiritigenin reverses epithelial-mesenchymal transition through modulation of the tgf-β/smad signaling pathway in endometrial cancer
AU - Chen, Hsin Yuan
AU - Chiang, Yi Fen
AU - Huang, Jia Syuan
AU - Huang, Tsui Chin
AU - Shih, Yin Hwa
AU - Wang, Kai Lee
AU - Ali, Mohamed
AU - Hong, Yong Han
AU - Shieh, Tzong Ming
AU - Hsia, Shih Min
N1 - Funding Information:
This research was funded from the Ministry of Science and Technology (MOST; Taiwan, China): the grants number (MOST 109-2314-B-038-059, 109-2628-B-038-015, MOST 109-2811-B-039-527, MOST 108-2314-B-039-009-MY3 and MOST 109-2320-B-254-001).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/3/2
Y1 - 2021/3/2
N2 - Endometrial cancer is a common gynecological cancer with a poor prognosis, mostly attributed to tumor metastasis. Epithelial–mesenchymal transition (EMT) can be mediated via transforming growth factor beta (TGF-β) signaling pathway, facilitating the ability of cancer cell invasion and migration. Isoliquiritigenin (ISL) is a flavonoid derived from licorice with reported antineoplastic activities. This study aims to investigate the anti-metastatic potential of ISL on endometrial cancer both in vitro and in vivo. First, human endometrial cancer cell lines (HEC-1A, Ishikawa, and RL95-2) were treated with ISL and then subjected to functional assays such as migration assay as well as molecular analyses including immunoblotting, immune fluorescence and RT-qPCR. In addition, HEC1A-LUC cells were implanted into female nude mice and treated with ISL by intraperitoneal injection for four weeks. Results showed that ISL inhibited cell migration and reversed the effect of TGF-β on the expression of E-cadherin, N-cadherin, vimentin, α-SMA, p-Smad3, and TWIST1/2 In vitro. Interestingly, In vivo study revealed that ISL reduced peritoneal dissemination and serum level of TGF-β1, as well as decreased the expression levels of N-cadherin, p-Smad2/3, TWIST1/2, while increased E-cadherin. Overall, ISL reverses the EMT through targeting the TGF-β/Smad signaling pathway and features a potential therapeutic treatment for metastatic endometrial cancer.
AB - Endometrial cancer is a common gynecological cancer with a poor prognosis, mostly attributed to tumor metastasis. Epithelial–mesenchymal transition (EMT) can be mediated via transforming growth factor beta (TGF-β) signaling pathway, facilitating the ability of cancer cell invasion and migration. Isoliquiritigenin (ISL) is a flavonoid derived from licorice with reported antineoplastic activities. This study aims to investigate the anti-metastatic potential of ISL on endometrial cancer both in vitro and in vivo. First, human endometrial cancer cell lines (HEC-1A, Ishikawa, and RL95-2) were treated with ISL and then subjected to functional assays such as migration assay as well as molecular analyses including immunoblotting, immune fluorescence and RT-qPCR. In addition, HEC1A-LUC cells were implanted into female nude mice and treated with ISL by intraperitoneal injection for four weeks. Results showed that ISL inhibited cell migration and reversed the effect of TGF-β on the expression of E-cadherin, N-cadherin, vimentin, α-SMA, p-Smad3, and TWIST1/2 In vitro. Interestingly, In vivo study revealed that ISL reduced peritoneal dissemination and serum level of TGF-β1, as well as decreased the expression levels of N-cadherin, p-Smad2/3, TWIST1/2, while increased E-cadherin. Overall, ISL reverses the EMT through targeting the TGF-β/Smad signaling pathway and features a potential therapeutic treatment for metastatic endometrial cancer.
KW - Endometrial cancer
KW - Epithelial–mesenchymal transition
KW - Isoliquiritigenin
KW - Metastasis
KW - Transforming growth factor beta
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U2 - 10.3390/cancers13061236
DO - 10.3390/cancers13061236
M3 - Article
AN - SCOPUS:85102185180
SN - 2072-6694
VL - 13
SP - 1
EP - 20
JO - Cancers
JF - Cancers
IS - 6
M1 - 1236
ER -
