Kwon Hee Jung, Lee Ga Seul, Moon Jeong Hee, Jung Joohee
College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea.
Core Research Facility & Analysis Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon 34141, Republic of Korea.
Cancers (Basel). 2025 Aug 11;17(16):2623. doi: 10.3390/cancers17162623.
: Liver cancer is a common cause of cancer-related deaths among men and women globally. A disintegrin and metalloproteinase with thrombospondin motif 1 (ADAMST1) has been associated with various cancers, including prostate, esophageal, renal, and breast cancers. However, its role in liver cancer remains unclear. The aim of this study was to investigate the relationship between G protein-coupled estrogen (GPER) activation via its agonist, G1, and ADAMTS1 in suppressing liver cancer metastasis. : Following preliminary assessment of Hep3B, Huh7, and SK-Hep-1 cells, SK-Hep-1 cells were selected owing to their elevated GPER expression and reduced cell viability. Cells were subjected to flow cytometry, RNA sequencing, and proteomics analyses. We established an SK-Hep-1 xenograft model for in vivo analysis. : We observed G1-induced G2-M phase cell cycle arrest, increased p53 and p21, and decreased cell cycle-related factors. In vivo, G1 significantly inhibited tumor growth and increased p53 protein expression. ADAMTS1, a metastasis regulator, was significantly upregulated by G1. G1 reduced the proliferating cell nuclear antigen and increased E-cadherin expression in SK-Hep-1 cells and in vivo. Tumor invasion was reduced with G1 and ADAMTS1 expression. In vivo, G1 reduced liver metastasis, increased E-cadherin, and decreased vimentin and proliferating cell nuclear antigen in primary tumor tissues and increased ADAMTS1 at the tumor edge. : GPER agonists, such as G1, show potential for suppressing liver cancer progression and metastasis.
肝癌是全球男性和女性癌症相关死亡的常见原因。含血小板反应蛋白基序的解聚素和金属蛋白酶1（ADAMST1）与包括前列腺癌、食管癌、肾癌和乳腺癌在内的多种癌症有关。然而，其在肝癌中的作用仍不清楚。本研究的目的是探讨通过其激动剂G1激活G蛋白偶联雌激素（GPER）与ADAMTS1在抑制肝癌转移中的关系。：在对Hep3B、Huh7和SK-Hep-1细胞进行初步评估后，由于SK-Hep-1细胞的GPER表达升高且细胞活力降低，因此选择了该细胞。对细胞进行流式细胞术、RNA测序和蛋白质组学分析。我们建立了一个SK-Hep-1异种移植模型用于体内分析。：我们观察到G1诱导G2-M期细胞周期停滞，p53和p21增加，细胞周期相关因子减少。在体内，G1显著抑制肿瘤生长并增加p53蛋白表达。转移调节因子ADAMTS1被G1显著上调。G1降低了SK-Hep-1细胞和体内增殖细胞核抗原的表达，并增加了E-钙黏蛋白的表达。G1和ADAMTS1表达降低了肿瘤侵袭。在体内，G1减少了肝转移，增加了原发性肿瘤组织中的E-钙黏蛋白，降低了波形蛋白和增殖细胞核抗原，并增加了肿瘤边缘的ADAMTS1。：GPER激动剂，如G1，在抑制肝癌进展和转移方面显示出潜力。
