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提取物通过诱导p53介导的细胞凋亡抑制人结肠直肠癌HT-29细胞的生长。

Extract Inhibits the Growth of Human Colorectal Cancer HT-29 Cells by Inducing p53-Mediated Apoptosis.

作者信息

Wu Rui, Zhao Jiajia, Wei Panhong, Tang Minghai, Ma Ziyan, Zhao Yunyan, Du Leilei, Wan Li

机构信息

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China.

出版信息

Pharmaceuticals (Basel). 2023 Sep 19;16(9):1325. doi: 10.3390/ph16091325.

DOI:10.3390/ph16091325
PMID:37765133
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10537627/
Abstract

Colorectal cancer (CRC) is a prevalent malignancy of the digestive tract with the second highest mortality rate globally. is a widely used traditional medicinal plant, exhibiting antitumor activity against various tumor cells. At present, research on the effect of on CRC is limited to in vitro cytotoxicity, lacking comprehensive mechanism investigations. This study aimed to explore the inhibitory effect and mechanism of extract (PNE) on HT-29 cells. Firstly, we identified the chemical components of PNE. Then, MTT assay, colony formation assay, JC-1 staining, and flow cytometry were used to analyze the effect of PNE on HT-29 cells in vitro. A xenograft model, histopathological examination, immunohistochemistry, and western blot were used to evaluate the tumor growth inhibitory activity and mechanism of PNE in vivo. The results indicated that PNE could inhibit cell proliferation and colony formation, reduce mitochondrial membrane potential, induce cell apoptosis in vitro, and inhibit tumor growth in vivo. Furthermore, PNE could regulate p53 and its downstream proteins, and subsequently activate the caspase-3 pathway. In summary, PNE probably induced apoptosis of HT-29 cells through the mitochondrial pathway mediated by p53. All these results suggested that PNE might be a potential natural-origin anti-CRC drug candidate.

摘要

结直肠癌(CRC)是一种常见的消化道恶性肿瘤,在全球死亡率排名第二。[此处原文缺失植物名称]是一种广泛使用的传统药用植物,对多种肿瘤细胞具有抗肿瘤活性。目前,关于[此处原文缺失植物名称]对CRC影响的研究仅限于体外细胞毒性,缺乏全面的机制研究。本研究旨在探讨[此处原文缺失植物名称]提取物(PNE)对HT - 29细胞的抑制作用及其机制。首先,我们鉴定了PNE的化学成分。然后,采用MTT法、集落形成试验、JC - 1染色和流式细胞术分析PNE对HT - 29细胞的体外作用。利用异种移植模型、组织病理学检查、免疫组织化学和蛋白质印迹法评估PNE在体内的肿瘤生长抑制活性及其机制。结果表明,PNE可抑制细胞增殖和集落形成,降低线粒体膜电位,诱导体外细胞凋亡,并抑制体内肿瘤生长。此外,PNE可调节p53及其下游蛋白,并随后激活caspase - 3途径。综上所述,PNE可能通过p53介导的线粒体途径诱导HT - 29细胞凋亡。所有这些结果表明,PNE可能是一种潜在的天然来源抗CRC候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/d88678619e06/pharmaceuticals-16-01325-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/4777b7c97a18/pharmaceuticals-16-01325-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/1497d22d9927/pharmaceuticals-16-01325-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/187874e449df/pharmaceuticals-16-01325-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/4391a3ef58db/pharmaceuticals-16-01325-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/637803621798/pharmaceuticals-16-01325-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/c5f74b322a30/pharmaceuticals-16-01325-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/d88678619e06/pharmaceuticals-16-01325-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/4777b7c97a18/pharmaceuticals-16-01325-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/1497d22d9927/pharmaceuticals-16-01325-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/187874e449df/pharmaceuticals-16-01325-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/4391a3ef58db/pharmaceuticals-16-01325-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/637803621798/pharmaceuticals-16-01325-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/c5f74b322a30/pharmaceuticals-16-01325-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9980/10537627/d88678619e06/pharmaceuticals-16-01325-g007.jpg

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