OSU-03012 Disrupts Akt Signaling and Prevents Endometrial Carcinoma Progression in vitro and in vivo.
Purpose
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.
['Ding|Leilei|L|', 'Ren|Chenchen|C|', 'Yang|Li|L|', 'Wu|Zimeng|Z|', 'Li|Feiyan|F|', 'Jiang|Dongyuan|D|', 'Zhu|Yuanhang|Y|', 'Lu|Jie|J|']
D000284:Administration, Oral D000818:Animals D000970:Antineoplastic Agents D017209:Apoptosis D002453:Cell Cycle D049109:Cell Proliferation D002470:Cell Survival D004354:Drug Screening Assays, Antitumor D016889:Endometrial Neoplasms D005260:Female D006801:Humans D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D009374:Neoplasms, Experimental D047428:Protein Kinase Inhibitors D051057:Proto-Oncogene Proteins c-akt D011720:Pyrazoles D015398:Signal Transduction D013449:Sulfonamides D014407:Tumor Cells, Cultured
OSU-03012 Akt signaling endometrial carcinoma the mitochondrial apoptosis pathway