OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo
Leilei Ding, Chenchen Ren, Li Yang, Zimeng Wu, Feiyan Li, Dongyuan Jiang, Yuanhang Zhu, Jie Lu Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Chenchen Ren; Li YangThe Third Affiliat...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2021-04-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/osu-03012-disrupts-akt-signaling-and-prevents-endometrial-carcinoma-pr-peer-reviewed-fulltext-article-DDDT |
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| author | Ding L Ren C Yang L Wu Z Li F Jiang D Zhu Y Lu J |
| author_facet | Ding L Ren C Yang L Wu Z Li F Jiang D Zhu Y Lu J |
| author_sort | Ding L |
| collection | DOAJ |
| description | Leilei Ding, Chenchen Ren, Li Yang, Zimeng Wu, Feiyan Li, Dongyuan Jiang, Yuanhang Zhu, Jie Lu Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Chenchen Ren; Li YangThe Third Affiliated Hospital of Zhengzhou University, No. 7, Front Kangfu Street, Zhengzhou, Henan Province, People’s Republic of ChinaTel +8613939057999; +8618697336662Email zdsfy_renchenchen@163.com; zdsfyyangli@163.comPurpose: OSU-03012 is a celecoxib derivative lacking cyclooxygenase-2 inhibitory activity and a potent PDK1 inhibitor which has been shown to inhibit tumor growth in various ways. However, the role of OSU-03012 in endometrial carcinoma (EC) in which the PI3K/Akt signaling pathway highly activated has not been studied. Here, we determined the potency of OSU-03012 in suppressing EC progression in vitro and in vivo, and studied the underlined mechanisms.Methods: The human EC Ishikawa and HEC-1A cells were used as the in vitro models. CCK8 assay and flow cytometry were conducted to evaluate cell proliferation, cell cycle progression, and apoptosis. The metastatic ability was evaluated using the transwell migration assay. The Ishikawa xenograft tumor model was used to study the inhibitory effects of OSU-03012 on EC growth in vivo. Western blot analysis was performed to evaluate expressions of the cell cycle and apoptosis associated proteins.Results: OSU-03012 could inhibit the progression of EC both in vitro and in vivo by disrupting Akt signaling. It reduced the metastatic ability of EC, led to G2/M cell cycle arrest and induced apoptosis via the mitochondrial apoptosis pathway.Conclusion: Our data indicated that OSU-03012 could inhibit the progression of EC in vitro and in vivo. It can potentially be used as the targeted drug for the treatment of EC by inhibiting Akt signaling.Keywords: OSU-03012, endometrial carcinoma, Akt signaling, the mitochondrial apoptosis pathway |
| first_indexed | 2024-12-16T11:06:48Z |
| format | Article |
| id | doaj.art-bfa7e680ae11478da51541e6d403de7d |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-16T11:06:48Z |
| publishDate | 2021-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-bfa7e680ae11478da51541e6d403de7d2022-12-21T22:33:51ZengDove Medical PressDrug Design, Development and Therapy1177-88812021-04-01Volume 151797181064401OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivoDing LRen CYang LWu ZLi FJiang DZhu YLu JLeilei Ding, Chenchen Ren, Li Yang, Zimeng Wu, Feiyan Li, Dongyuan Jiang, Yuanhang Zhu, Jie Lu Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Chenchen Ren; Li YangThe Third Affiliated Hospital of Zhengzhou University, No. 7, Front Kangfu Street, Zhengzhou, Henan Province, People’s Republic of ChinaTel +8613939057999; +8618697336662Email zdsfy_renchenchen@163.com; zdsfyyangli@163.comPurpose: OSU-03012 is a celecoxib derivative lacking cyclooxygenase-2 inhibitory activity and a potent PDK1 inhibitor which has been shown to inhibit tumor growth in various ways. However, the role of OSU-03012 in endometrial carcinoma (EC) in which the PI3K/Akt signaling pathway highly activated has not been studied. Here, we determined the potency of OSU-03012 in suppressing EC progression in vitro and in vivo, and studied the underlined mechanisms.Methods: The human EC Ishikawa and HEC-1A cells were used as the in vitro models. CCK8 assay and flow cytometry were conducted to evaluate cell proliferation, cell cycle progression, and apoptosis. The metastatic ability was evaluated using the transwell migration assay. The Ishikawa xenograft tumor model was used to study the inhibitory effects of OSU-03012 on EC growth in vivo. Western blot analysis was performed to evaluate expressions of the cell cycle and apoptosis associated proteins.Results: OSU-03012 could inhibit the progression of EC both in vitro and in vivo by disrupting Akt signaling. It reduced the metastatic ability of EC, led to G2/M cell cycle arrest and induced apoptosis via the mitochondrial apoptosis pathway.Conclusion: Our data indicated that OSU-03012 could inhibit the progression of EC in vitro and in vivo. It can potentially be used as the targeted drug for the treatment of EC by inhibiting Akt signaling.Keywords: OSU-03012, endometrial carcinoma, Akt signaling, the mitochondrial apoptosis pathwayhttps://www.dovepress.com/osu-03012-disrupts-akt-signaling-and-prevents-endometrial-carcinoma-pr-peer-reviewed-fulltext-article-DDDTosu03012endometrial carcinoma (ec)akt signalingthe mitochondrial apoptosis pathway |
| spellingShingle | Ding L Ren C Yang L Wu Z Li F Jiang D Zhu Y Lu J OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo Drug Design, Development and Therapy osu03012 endometrial carcinoma (ec) akt signaling the mitochondrial apoptosis pathway |
| title | OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo |
| title_full | OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo |
| title_fullStr | OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo |
| title_full_unstemmed | OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo |
| title_short | OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo |
| title_sort | osu 03012 disrupts akt signaling and prevents endometrial carcinoma progression in vitro and in vivo |
| topic | osu03012 endometrial carcinoma (ec) akt signaling the mitochondrial apoptosis pathway |
| url | https://www.dovepress.com/osu-03012-disrupts-akt-signaling-and-prevents-endometrial-carcinoma-pr-peer-reviewed-fulltext-article-DDDT |
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