Glycolysis is suppressed by DCZ0801-induced inactivation of the Akt/mTOR pathway in Multiple Myeloma

DCZ0801 诱导的多发性骨髓瘤 Akt/mTOR 通路失活可抑制糖酵解

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作者:Qilin Feng, Qingchun Yao, Bo Li, Yongsheng Xie, Hui Zhang, Zhijian Xu, Kang Lu, Ke Hu, Yao Cheng, Bingqing Shi, Cheng Huang, Liping Li, Xiaosong Wu, Shanxi You, Jumei Shi, Weiliang Zhu

Abstract

Multiple myeloma (MM) is a highly invasive and incurable plasma cell malignant disease with frequent recurrence. DCZ0801 is a natural compound synthesized from osalmide and pterostilbene and has few adverse effects. Here, we aimed to observe the therapeutic effects of DCZ0801 on myeloma cells and clarify the specific molecular mechanism underlying its anti-tumor activity. The Cell Counting Kit-8 assay, apoptosis detection, cell cycle analysis, western blot analysis, and tumor xenograft models were used to determine the effect of DCZ0801 treatment both in vivo and in vitro. We revealed that DCZ0801 treatment suppressed MM cell survival by inducing apoptosis and blocking the cell cycle at S phase. Deranged glycolysis and downregulated Akt/mTOR pathway may also be responsible for cell proliferation inhibition. Moreover, DCZ0801 treatment could remarkably reduce the tumor size in the xenograft mouse model. Therefore these findings indicate that DCZ0801 can be used as a novel therapeutic drug for patients suffering from multiple myeloma.

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