Bazedoxifene, a GP130 Inhibitor, Modulates EMT Signaling and Exhibits Antitumor Effects in HPV-Positive Cervical Cancer
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 neede...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-08-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/22/16/8693 |
id |
doaj-5eab9a90b1364de1b7f534432e4ed764 |
---|---|
record_format |
Article |
spelling |
doaj-5eab9a90b1364de1b7f534432e4ed7642021-08-26T13:52:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-01228693869310.3390/ijms22168693Bazedoxifene, a GP130 Inhibitor, Modulates EMT Signaling and Exhibits Antitumor Effects in HPV-Positive Cervical CancerLeekyung Kim0Sun-Ae Park1Hyemin Park2Heejung Kim3Tae-Hwe Heo4Laboratory of Pharmacoimmunology, Integrated Research Institute of Pharmaceutical Sciences and BK21 FOUR Team for Advanced Program for SmartPharma Leaders, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si 14662, Gyeonggi-do, KoreaLaboratory of Pharmacoimmunology, Integrated Research Institute of Pharmaceutical Sciences and BK21 FOUR Team for Advanced Program for SmartPharma Leaders, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si 14662, Gyeonggi-do, KoreaLaboratory of Pharmacoimmunology, Integrated Research Institute of Pharmaceutical Sciences and BK21 FOUR Team for Advanced Program for SmartPharma Leaders, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si 14662, Gyeonggi-do, KoreaLaboratory of Pharmacoimmunology, Integrated Research Institute of Pharmaceutical Sciences and BK21 FOUR Team for Advanced Program for SmartPharma Leaders, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si 14662, Gyeonggi-do, KoreaLaboratory of Pharmacoimmunology, Integrated Research Institute of Pharmaceutical Sciences and BK21 FOUR Team for Advanced Program for SmartPharma Leaders, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si 14662, Gyeonggi-do, KoreaPersistent 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.https://www.mdpi.com/1422-0067/22/16/8693BazedoxifeneHPV-positivecervix cancerEMT signaling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Leekyung Kim Sun-Ae Park Hyemin Park Heejung Kim Tae-Hwe Heo |
spellingShingle |
Leekyung Kim Sun-Ae Park Hyemin Park Heejung Kim Tae-Hwe Heo Bazedoxifene, a GP130 Inhibitor, Modulates EMT Signaling and Exhibits Antitumor Effects in HPV-Positive Cervical Cancer International Journal of Molecular Sciences Bazedoxifene HPV-positive cervix cancer EMT signaling |
author_facet |
Leekyung Kim Sun-Ae Park Hyemin Park Heejung Kim Tae-Hwe Heo |
author_sort |
Leekyung Kim |
title |
Bazedoxifene, a GP130 Inhibitor, Modulates EMT Signaling and Exhibits Antitumor Effects in HPV-Positive Cervical Cancer |
title_short |
Bazedoxifene, a GP130 Inhibitor, Modulates EMT Signaling and Exhibits Antitumor Effects in HPV-Positive Cervical Cancer |
title_full |
Bazedoxifene, a GP130 Inhibitor, Modulates EMT Signaling and Exhibits Antitumor Effects in HPV-Positive Cervical Cancer |
title_fullStr |
Bazedoxifene, a GP130 Inhibitor, Modulates EMT Signaling and Exhibits Antitumor Effects in HPV-Positive Cervical Cancer |
title_full_unstemmed |
Bazedoxifene, a GP130 Inhibitor, Modulates EMT Signaling and Exhibits Antitumor Effects in HPV-Positive Cervical Cancer |
title_sort |
bazedoxifene, a gp130 inhibitor, modulates emt signaling and exhibits antitumor effects in hpv-positive cervical cancer |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-08-01 |
description |
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. |
topic |
Bazedoxifene HPV-positive cervix cancer EMT signaling |
url |
https://www.mdpi.com/1422-0067/22/16/8693 |
work_keys_str_mv |
AT leekyungkim bazedoxifeneagp130inhibitormodulatesemtsignalingandexhibitsantitumoreffectsinhpvpositivecervicalcancer AT sunaepark bazedoxifeneagp130inhibitormodulatesemtsignalingandexhibitsantitumoreffectsinhpvpositivecervicalcancer AT hyeminpark bazedoxifeneagp130inhibitormodulatesemtsignalingandexhibitsantitumoreffectsinhpvpositivecervicalcancer AT heejungkim bazedoxifeneagp130inhibitormodulatesemtsignalingandexhibitsantitumoreffectsinhpvpositivecervicalcancer AT taehweheo bazedoxifeneagp130inhibitormodulatesemtsignalingandexhibitsantitumoreffectsinhpvpositivecervicalcancer |
_version_ |
1721192582154813440 |