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茄解碱通过激活AMPK/FOXO3A轴抑制急性单核细胞白血病的增殖。

Solasonine Suppresses the Proliferation of Acute Monocytic Leukemia Through the Activation of the AMPK/FOXO3A Axis.

作者信息

Zhang Hong, Tian Fang, Jiang Pengjun, Qian Shushu, Dai Xingbin, Ma Bangyun, Wang Mengya, Dai Huibo, Sha Xiaocao, Yang Zhongfa, Zhu Xuejun, Sun Xuemei

机构信息

Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Institute of Clinical Medicine, Weifang Medical University, Weifang, China.

出版信息

Front Oncol. 2021 Jan 29;10:614067. doi: 10.3389/fonc.2020.614067. eCollection 2020.

Abstract

Solasonine, the main active ingredient of ., has been reported to exert extensive antitumor activity. However, the antitumor effects in acute monocytic leukemia and the exact mechanisms involved are unknown. In this study, we investigated the role of solasonine on inhibiting the progression of acute monocytic leukemia. Our findings showed that solasonine inhibited the proliferation of acute monocytic leukemic cell lines (THP-1 and MV4-11) . Solasonine promoted apoptosis and induced cell cycle arrest in the G2/M phase. Analysis of RNA-seq data suggested that solasonine correlated with increased expression of genes in the AMPK/FOXO3A pathway. Inhibition of AMPK with compound C followed by treatment with solasonine showed that solasonine reduced apoptosis, caused less cell cycle arrest, and inactivated the AMPK/FOXO3A axis in THP-1 and MV4-11 cells. Solasonine also inhibited tumor growth by the activation of the AMPK/FOXO3A axis. In conclusion, solasonine inhibited the progress of acute monocytic leukemia and and triggered the apoptosis and cell cycle arrest in the G2/M phase by upregulating the AMPK/FOXO3A pathway.

摘要

澳洲茄碱是……的主要活性成分,据报道具有广泛的抗肿瘤活性。然而,其对急性单核细胞白血病的抗肿瘤作用及具体机制尚不清楚。在本研究中,我们探讨了澳洲茄碱在抑制急性单核细胞白血病进展中的作用。我们的研究结果表明,澳洲茄碱可抑制急性单核细胞白血病细胞系(THP-1和MV4-11)的增殖。澳洲茄碱促进细胞凋亡并诱导细胞周期阻滞于G2/M期。RNA测序数据分析表明,澳洲茄碱与AMPK/FOXO3A通路中基因表达增加相关。先用化合物C抑制AMPK,再用澳洲茄碱处理,结果显示澳洲茄碱可减少THP-1和MV4-11细胞的凋亡,导致较少的细胞周期阻滞,并使AMPK/FOXO3A轴失活。澳洲茄碱还通过激活AMPK/FOXO3A轴抑制肿瘤生长。总之,澳洲茄碱通过上调AMPK/FOXO3A通路抑制急性单核细胞白血病进展,并引发G2/M期细胞凋亡和细胞周期阻滞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f1f/7879981/2d19f604be46/fonc-10-614067-g001.jpg

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