Arabic Arabic English English French French German German
dark

Targeting AKT with oridonin inhibits growth of esophageal squamous cell carcinoma.

PMID: 

Mol Cancer Ther. 2018 07 ;17(7):1540-1553. Epub 2018 Apr 25. PMID: 29695636

Abstract Title: 

Targeting AKT with Oridonin Inhibits Growth of Esophageal Squamous Cell Carcinomaand Patient-Derived Xenografts.

Abstract: 

Overexpression or activation of AKT is very well known to control cell growth, survival, and gene expression in solid tumors. Oridonin, an inflammatory medical and diterpenoid compound isolated from, has exhibited various pharmacologic and physiologic properties, including antitumor, antibacterial, and anti-inflammatory effects. In this study, we demonstrated that oridonin is an inhibitor of AKT and suppresses proliferation of esophageal squamous cell carcinoma (ESCC)andThe role of AKT in ESCC was studied using immuno-histochemical analysis of a tumor microarray, the effect of AKT knockdown on cell growth, and treatment of cells with MK-2206, an AKT inhibitor. Oridonin blocked AKT kinase activity and interacted with the ATP-binding pocket of AKT. It inhibited growth of KYSE70, KYSE410, and KYSE450 esophageal cancer cells in a time- and concentration-dependent manner. Oridonin induced arrest of cells in the G-M cell-cycle phase, stimulated apoptosis, and increased expression of apoptotic biomarkers, including cleaved PARP, caspase-3, caspase-7, and Bimin ESCC cell lines. Mechanistically, we found that oridonin diminished the phosphorylation and activation of AKT signaling. Furthermore, a combination of oridonin and 5-fluorouracil or cisplatin (clinical chemotherapeutic agents) enhanced the inhibition of ESCC cell growth. The effects of oridonin were verified in patient-derived xenograft tumors expressing high levels of AKT. In summary, our results indicate that oridonin acts as an AKT inhibitor to suppress the growth of ESCC by attenuating AKT signaling..

read more

Read More

Total
0
Shares
Leave a Reply

Your email address will not be published. Required fields are marked *

Previous Post

Oridonin inhibits aberrant AKT activation in breast cancer.

Next Post

Oridonin induces apoptosis in oral squamous cell carcinoma.

Related Posts
Total
0
Share