The G-Protein-Coupled Estrogen Receptor Agonist G-1 Mediates Antitumor Effects by Activating Apoptosis Pathways and Regulating Migration and Invasion in Cervical Cancer Cells

蛋白偶联雌激素受体激动剂 G-1 通过激活凋亡途径和调节宫颈癌细胞的迁移和侵袭来介导抗肿瘤作用

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作者:Abigail Gaxiola-Rubio, Luis Felipe Jave-Suárez, Christian David Hernández-Silva, Adrián Ramírez-de-Arellano, Julio César Villegas-Pineda, Marisa de Jesús Lizárraga-Ledesma, Moisés Ramos-Solano, Carlos Daniel Diaz-Palomera, Ana Laura Pereira-Suárez

Conclusions

GPER is a promising prognostic marker due to its ability to activate apoptosis and inhibit proliferation without promoting migration/invasion in CC cells. G-1 could potentially be a tool in the treatment of this neoplasia.

Methods

Transcriptome analysis was performed to identify G-1-enriched pathways in SiHa cells. We evaluated cell migration, invasion, and the expression of associated proteins in SiHa, HaCaT-16E6, and HaCaT-16E7 cells using various assays.

Results

Transcriptome analysis revealed pathways associated with proliferation/apoptosis (TNF-α signaling, UV radiation response, mitotic spindle formation, G2/M cell cycle, UPR, and IL-6/JAK/STAT), cellular metabolism (oxidative phosphorylation), and cell migration (angiogenesis, EMT, and TGF-α signaling) in SiHa cells. Key differentially expressed genes included PTGS2 (pro/antitumor), FOSL1, TNFRSF9, IL1B, DIO2, and PHLDA1 (antitumor), along with under-expressed genes with pro-tumor effects that may inhibit proliferation. Additionally, DKK1 overexpression suggested inhibition of cell migration. G-1 increased vimentin expression in SiHa cells and reduced it in HaCaT-16E6 and HaCaT-16E7 cells. However, G-1 did not affect α-SMA expression or cell migration in any of the cell lines but increased invasion in HaCaT-16E7 cells. Conclusions: GPER is a promising prognostic marker due to its ability to activate apoptosis and inhibit proliferation without promoting migration/invasion in CC cells. G-1 could potentially be a tool in the treatment of this neoplasia.

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