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Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

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

Abstract Author(s):

Mengqiu Song, Xuejiao Liu, Kangdong Liu, Ran Zhao, Hai Huang, Yuanyuan Shi, Man Zhang, Silei Zhou, Hua Xie, Hanyong Chen, Yin Li, Yan Zheng, Qiong Wu, Fangfang Liu, Enmin Li, Ann M Bode, Zigang Dong, Mee-Hyun Lee

Article Affiliation:

Mengqiu Song

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..

Study Type : Animal Study

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