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胡椒乙胺通过调节氨基酸代谢抑制肝癌细胞生长和增殖,并抑制肿瘤发生。

Cepharanthine inhibits hepatocellular carcinoma cell growth and proliferation by regulating amino acid metabolism and suppresses tumorigenesis .

机构信息

National Innovation and Attracting Talents "111" base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.

Chongqing Engineering Research Center of Antitumor Natural Drugs, Chongqing Three Gorges Medical College, Chongqing 400030, China.

出版信息

Int J Biol Sci. 2021 Oct 22;17(15):4340-4352. doi: 10.7150/ijbs.64675. eCollection 2021.

Abstract

Cepharanthine (CEP), a natural compound extracted from Hayata, has been found to have the potential to treat a variety of tumors in recent years. This study aims to evaluate the anti-hepatocellular carcinoma (HCC) effect of CEP and determine its in-depth mechanism. In this study, Hep3B and HCCLM3 cells were selected to evaluate the antitumor effects of CEP , whereas tumor xenograft in nude mice was performed to make anti-tumor assessment. RNA-sequence (RNA-seq) was used to identify possible molecular targets and pathways. Further, gas chromatography mass spectrometry (GC-MS) was performed to assess the differential metabolites involved in mediating the effect of CEP on the HCC cell line. Our results showed that CEP treatment resulted in the dose-dependent inhibition of cell viability, migration, and proliferation and could also induce apoptosis in HCC cells. RNA-seq following CEP treatment identified 168 differentially expressed genes (DEGs), which were highly enriched in metabolism-associated pathways. In addition, CEP down-regulated many metabolites through the amino acid metabolism pathway. experiment showed that CEP significantly suppressed tumor growth. Our results indicate that CEP has significant antitumor effects and has the potential to be a candidate drug for HCC treatment.

摘要

石蒜碱(CEP)是从石蒜中提取的一种天然化合物,近年来被发现具有治疗多种肿瘤的潜力。本研究旨在评估 CEP 对肝癌(HCC)的治疗作用,并确定其深入的作用机制。本研究选择 Hep3B 和 HCCLM3 细胞来评估 CEP 的抗肿瘤作用,而裸鼠肿瘤异种移植则用于进行抗肿瘤评估。RNA 测序(RNA-seq)用于鉴定可能的分子靶点和途径。此外,还进行了气相色谱-质谱联用(GC-MS)分析,以评估参与介导 CEP 对 HCC 细胞系作用的差异代谢物。研究结果表明,CEP 处理导致细胞活力、迁移和增殖的剂量依赖性抑制,并且还可以诱导 HCC 细胞凋亡。CEP 处理后的 RNA-seq 鉴定出 168 个差异表达基因(DEGs),这些基因高度富集在代谢相关途径中。此外,CEP 通过氨基酸代谢途径下调了许多代谢物。实验表明 CEP 显著抑制了肿瘤生长。我们的研究结果表明,CEP 具有显著的抗肿瘤作用,有望成为 HCC 治疗的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5201/8579440/7b49cfb8dd54/ijbsv17p4340g001.jpg

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