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白茅根提取物对CD24基因的抑制和TIMP-4基因的上调可通过抑制PI3K/Akt/snail信号通路和阻断上皮-间质转化来预防CaSki细胞的转移。

CD24 gene inhibition and TIMP-4 gene upregulation by Imperata cylindrica's root extract prevents metastasis of CaSki cells via inhibiting PI3K/Akt/snail signaling pathway and blocking EMT.

作者信息

Nayim Paul, Mbaveng Armelle T, Sanjukta Mukherjee, Rikesh Jain, Kuete Victor, Sudhir Krishna

机构信息

Department of Biochemistry, University of Dschang, Dschang, Cameroon; National Centre for Biological Sciences - Tata Institute of Fundamental Research (TIFR), Bangalore, India.

Department of Biochemistry, University of Dschang, Dschang, Cameroon.

出版信息

J Ethnopharmacol. 2021 Jul 15;275:114111. doi: 10.1016/j.jep.2021.114111. Epub 2021 Apr 10.

DOI:10.1016/j.jep.2021.114111
PMID:33848610
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Imperata cylindrica (L.) Raeusch (Gramineae) is a medicinal spice traditionally used in the treatment of hypertension and cancer.

AIM OF THE STUDY

To assess the anti-metastatic potential of the methanol extract of I. cylindrica roots and determined its mechanisms of action.

MATERIAL AND METHODS

The growth inhibition activity of I. cylindrica root extract in vitro and in vivo in human cervical cancer. The scratch assay and Boyden Chamber assay were used to determine the anti-migrative and anti-invasion actions of the plant extract. The whole-genome gene expression profiling using RNA-Seq was performed to determine the differentially expressed genes in CaSki cells after exposure to I. cylindrica to identify its targeted genes related to metastasis. Using protein analysis (western blotting) and gene expression analysis (RTqPCR), the targeted pathways of the key genes that were initially identified with RNA-Seq, were evaluated.

RESULTS

I. cylindrica extract showed dose-dependent cytotoxicity in vitro and in vivo in mice bearing tumors. Furthermore, I. cylindrica root extract significantly inhibited cell migration and cell invasion. After the genome-wide transcriptome analysis, we found that important genes involved in cancer progression and metastasis of cervical cancer, that is, CD24 and TIMP-4 were significantly downregulated and upregulated, respectively. Moreover, I. cylindrica root extract significantly inhibited the PI3/AKT/Snail signaling pathway and blocked the EMT of CaSki cells.

CONCLUSION

These findings provide an anti-metastatic mechanism of action of I. cylindrica root extract toward the human cervical cancer suggesting that this plant maybe developed into selective chemotherapy.

摘要

民族药理学相关性

白茅(禾本科)是一种传统上用于治疗高血压和癌症的药用香料。

研究目的

评估白茅根甲醇提取物的抗转移潜力并确定其作用机制。

材料与方法

白茅根提取物在体外和体内对人宫颈癌的生长抑制活性。采用划痕试验和博伊登小室试验来确定植物提取物的抗迁移和抗侵袭作用。使用RNA测序进行全基因组基因表达谱分析,以确定暴露于白茅后CaSki细胞中差异表达的基因,从而识别其与转移相关的靶基因。通过蛋白质分析(蛋白质印迹法)和基因表达分析(实时定量聚合酶链反应),评估最初通过RNA测序鉴定的关键基因的靶向途径。

结果

白茅提取物在体外和体内对荷瘤小鼠均表现出剂量依赖性细胞毒性。此外,白茅根提取物显著抑制细胞迁移和细胞侵袭。在全基因组转录组分析后,我们发现参与宫颈癌进展和转移的重要基因,即CD24和TIMP-4分别显著下调和上调。此外,白茅根提取物显著抑制PI3/AKT/Snail信号通路并阻断CaSki细胞的上皮-间质转化。

结论

这些发现揭示了白茅根提取物对人宫颈癌的抗转移作用机制,表明这种植物可能发展成为选择性化疗药物。

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