Bazedoxifene, a GP130 Inhibitor, Modulates EMT Signaling and Exhibits Antitumor Effects in HPV-Positive Cervical Cancer

Autor: Hee Jung Kim, Sun-Ae Park, Hyemin Park, Leekyung Kim, Tae-Hwe Heo
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Indoles
Uterine Cervical Neoplasms
Mice
Cytokine Receptor gp130
Protein Interaction Maps
Phosphorylation
Biology (General)
STAT3
Spectroscopy
Cervical cancer
biology
HPV-positive
General Medicine
EMT signaling
Computer Science Applications
Drug repositioning
Chemistry
Female
medicine.drug
Signal Transduction
Epithelial-Mesenchymal Transition
medicine.drug_class
Cell Survival
QH301-705.5
Mice
Nude
Bazedoxifene
Catalysis
Article
Inorganic Chemistry
cervix cancer
In vivo
Cell Line
Tumor
medicine
Animals
Humans
Physical and Theoretical Chemistry
Molecular Biology
QD1-999
Cell Proliferation
business.industry
Interleukin-6
Organic Chemistry
Papillomavirus Infections
Drug Repositioning
Cancer
Glycoprotein 130
medicine.disease
Xenograft Model Antitumor Assays
Estrogen
Cancer research
biology.protein
business
HeLa Cells
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 8693, p 8693 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 16
ISSN: 1661-6596
1422-0067
Popis: Persistent HPV (Human Papillomavirus) infection is the primary cause of cervical cancer. Despite the development of the HPV vaccine to prevent infections, cervical cancer is still a fatal malignant tumor and metastatic disease, and it is often difficult to treat, so a new treatment strategy is needed. The FDA-approved drug Bazedoxifene is a novel inhibitor of protein–protein interactions between IL-6 and GP130. Multiple ligand simultaneous docking and drug repositioning approaches have demonstrated that an IL-6/GP130 inhibitor can act as a selective estrogen modulator. However, the molecular basis for GP130 activation in cervical cancer remains unclear. In this study, we investigated the anticancer properties of Bazedoxifene in HPV-positive cervical cancer cells. In vitro and in vivo experiments showed that Bazedoxifene inhibited cell invasion, migration, colony formation, and tumor growth in cervical cancer cells. We also confirmed that Bazedoxifene inhibits the GP130/STAT3 pathway and suppresses the EMT (Epithelial-mesenchymal transition) sub-signal. Thus, these data not only suggest a molecular mechanism by which the GP130/STAT3 pathway may promote cancer, but also may provide a basis for cervical cancer replacement therapy.
Databáze: OpenAIRE
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