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通过整合网络药理学分析与实验验证对L.提取物抗结直肠癌抗癌机制的研究

An Investigation of the Anticancer Mechanism of L. Extract Against Colorectal Cancer by Integrating a Network Pharmacological Analysis and Experimental Validation.

作者信息

Jeong Mibae, Chun Jaemoo, Park Sang-Min, Yeo Heerim, Na Se Won, Ha In Jin, Kim Bonglee, Jeong Mi-Kyung

机构信息

KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.

KIOM School, University of Science & Technology (UST), Daejeon 34054, Republic of Korea.

出版信息

Plants (Basel). 2025 Jan 18;14(2):263. doi: 10.3390/plants14020263.

DOI:10.3390/plants14020263
PMID:39861616
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11768342/
Abstract

L. has exhibited various pharmacological effects, yet its anticancer activities against colorectal cancer (CRC) and underlying molecular mechanisms remain unclear. This study investigated the anticancer properties of an ethanol extract of L. (CSE) against CRC cells, focusing on the identification of bioactive compounds and their mechanisms of action. A network pharmacology analysis was conducted to identify potential CRC targets and bioactive compounds of CSE, using LC-MS for compound identification. The anticancer effects of CSE were then validated through in vitro and in vivo models of CRC. The network pharmacological approach identified 87 overlapping genes between CSE targets and CRC-related genes, with protein-protein interaction analysis highlighting 33 key target genes. CSE inhibited cell proliferation in human CRC cell lines, including HCT 116, KM12SM, HT-29, and COLO 205, and induced apoptosis via caspase 3/7 activation. Western blot analyses confirmed the modulation of critical signaling pathways, including STAT3, AKT, and mitogen-activated protein kinases. Furthermore, CSE significantly suppressed tumor growth in MC38 CRC-bearing mice. These findings suggest that CSE possesses substantial potential as a natural anticancer agent for CRC treatment, highlighting the need for further exploration in therapeutic development.

摘要

L.已表现出多种药理作用,但其对结直肠癌(CRC)的抗癌活性及潜在分子机制仍不清楚。本研究调查了L.乙醇提取物(CSE)对CRC细胞的抗癌特性,重点是生物活性化合物的鉴定及其作用机制。进行了网络药理学分析以鉴定CSE的潜在CRC靶点和生物活性化合物,并使用液相色谱-质谱联用(LC-MS)进行化合物鉴定。然后通过CRC的体外和体内模型验证了CSE的抗癌作用。网络药理学方法确定了CSE靶点与CRC相关基因之间的87个重叠基因,蛋白质-蛋白质相互作用分析突出了33个关键靶基因。CSE抑制人CRC细胞系(包括HCT 116、KM12SM、HT-29和COLO 205)的细胞增殖,并通过激活半胱天冬酶3/7诱导细胞凋亡。蛋白质印迹分析证实了关键信号通路(包括信号转导和转录激活因子3(STAT3)、蛋白激酶B(AKT)和丝裂原活化蛋白激酶)的调节。此外,CSE显著抑制MC38荷CRC小鼠的肿瘤生长。这些发现表明,CSE作为一种用于CRC治疗的天然抗癌剂具有巨大潜力,突出了在治疗开发中进一步探索的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/6059ad031418/plants-14-00263-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/e5af226cee6f/plants-14-00263-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/67f88985a949/plants-14-00263-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/fc01db346f81/plants-14-00263-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/92c80c982549/plants-14-00263-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/ad6cf87df106/plants-14-00263-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/da7f7fa65c16/plants-14-00263-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/f24a4ffc11ba/plants-14-00263-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/dae43238c946/plants-14-00263-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/d1c8b12f1e0f/plants-14-00263-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/6059ad031418/plants-14-00263-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/e5af226cee6f/plants-14-00263-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/67f88985a949/plants-14-00263-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/fc01db346f81/plants-14-00263-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/92c80c982549/plants-14-00263-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/ad6cf87df106/plants-14-00263-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/da7f7fa65c16/plants-14-00263-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/f24a4ffc11ba/plants-14-00263-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/dae43238c946/plants-14-00263-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/d1c8b12f1e0f/plants-14-00263-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/11768342/6059ad031418/plants-14-00263-g010.jpg

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