G-Protein-Coupled Estrogen Receptor Antagonist G15 Decreases Estrogen-Induced Development of Non-Small Cell Lung Cancer
| Autor: | Xiang-ning Fu, Sheng Fan, Changyu Liu, Jianmiao Wang, Yongde Liao, Sheng Zhou, Jing Xiong, Man Zou |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Lung Neoplasms medicine.drug_class Estrogen receptor G-protein-coupled estrogen receptor (GPER) Non-small cell lung cancer (NSCLC) Adenocarcinoma Urethane Article Receptors G-Protein-Coupled Estrogen Receptor Antagonists Mice 03 medical and health sciences Estrogen-related receptor alpha E2 Carcinoma Non-Small-Cell Lung Cell Line Tumor G1 medicine Animals Estrogen Receptor beta Humans Benzodioxoles Fulvestrant Estrogen receptor beta Cell Proliferation Chemistry Cell growth G15 Estrogens General Medicine 030104 developmental biology Receptors Estrogen Oncology A549 Cells Estrogen Quinolines Cancer research Female GPER Signal Transduction medicine.drug |
| Zdroj: | Oncology Research |
| ISSN: | 0965-0407 |
| DOI: | 10.3727/096504017x15035795904677 |
| Popis: | G-protein-coupled estrogen receptor (GPER) was found to promote non-small cell lung cancer (NSCLC) by estrogen, indicating the potential necessity of inhibiting GPER by a selective antagonist. This study was performed to elucidate the function of GPER-selective inhibitor G15 in NSCLC development. Cytoplasmic GPER (cGPER) and nuclear GPER (nGPER) were detected by immunohistochemical analysis in NSCLC samples. The relation of GPER and estrogen receptor β (ERβ) expression and correlation between GPER, ERβ, and clinical factors were analyzed. The effects of activating GPER and function of G15 were analyzed in the proliferation of A549 and H1793 cell lines and development of urethane-induced adenocarcinoma. Overexpression of cGPER and nGPER was detected in 80.49% (120/150) and 52.00% (78/150) of the NSCLC samples. High expression of GPER was related with higher stages, poorer differentiation, and high expression of ERβ. The protein level of GPER in the A549 and H1793 cell lines was increased by treatment with E2, G1 (GPER agonist), or fulvestrant (Ful; ERβ antagonist) and decreased by G15. Administration with G15 reversed the E2- or G1-induced cell growth by inhibiting GPER. In urethane-induced adenocarcinoma mice, the number of tumor nodules and tumor index increased in the E2 or G1 group and decreased by treatment with G15. These findings demonstrate that using G15 to block GPER signaling may be considered as a new therapeutic target in NSCLC. |
| Databáze: | OpenAIRE |
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