Alkaloids of Aconiti Lateralis Radix Praeparata inhibit growth of non-small cell lung cancer by regulating PI3K/Akt-mTOR signaling and glycolysis

附子生物碱通过调节 PI3K/Akt-mTOR 信号转导和糖酵解抑制非小细胞肺癌的生长

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作者:Wen Zhang #, Shuhui Cai #, Lihong Qin #, Yaru Feng, Menglei Ding, Zichen Luo, Jinjun Shan, Liuqing Di

Abstract

Aconiti Lateralis Radix Praeparata (Fuzi in Chinese) is widely used in the clinical treatment of tumors. This study aims to explore the active fractions and underlying mechanisms of Fuzi in the treatment of non-small cell lung cancer (NSCLC). Fuzi alkaloids (FZA) is prepared and found to inhibit the growth of NSCLC both in vitro and in vivo significantly. A total of 53 alkaloids are identified in FZA by UPLC-Q-TOF-MS. Proteomics experiment show that 238 differentially expressed proteins regulated by FZA are involved in amino acid anabolism, pyrimidine metabolism and PI3K/Akt-mTOR signaling pathway. Metabolomics analyses identify 32 significant differential metabolites which are mainly involved in amino acid metabolism, TCA cycle and other pathways. Multi-omics research combined with molecular biological assays suggest that FZA might regulate glycolysis through PI3K/Akt-mTOR pathway to treat NSCLC. The study lays a foundation for the anti-cancer investigation of Fuzi and provides a possible scientific basis for its clinical application.

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