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可刺激人肝癌细胞生长的感染性幼虫提取物肽。

Peptide of Infective Larval Extract That Harnesses Growth of Human Hepatoma Cells.

机构信息

Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

出版信息

Front Cell Infect Microbiol. 2022 Apr 26;12:882608. doi: 10.3389/fcimb.2022.882608. eCollection 2022.

DOI:10.3389/fcimb.2022.882608
PMID:35558100
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9086976/
Abstract

, a tissue-dwelling helminth, causes human trichinellosis through ingestion of undercooked meat containing the parasite's infective larvae. However, benefits from infection have been documented: reduction of allergic diseases, inhibition of collagen-induced arthritis, delay of type 1 diabetes progression, and suppression of cancer cell proliferation. Since conventional cancer treatments have limited and unreliable efficacies with adverse side effects, novel adjunctive therapeutic agents and strategies are needed to enhance the overall treatment outcomes. This study aimed to validate the antitumor activity of infective larval extract (LE) and extricate the parasite-derived antitumor peptide. Extracts of infective larvae harvested from striated muscles of infected mice were prepared and tested for antitumor activity against three types of carcinoma cells: hepatocellular carcinoma HepG2, ovarian cancer SK-OV-3, and lung adenocarcinoma A549. The results showed that LE exerted the greatest antitumor effect on HepG2 cells. Proteomic analysis of the LE revealed 270 proteins. They were classified as cellular components, proteins involved in metabolic processes, and proteins with diverse biological functions. STRING analysis showed that most LE proteins were interconnected and played pivotal roles in various metabolic processes. analysis of anticancer peptides identified three candidates. Antitumor peptide 2 matched the hypothetical protein T01_4238 of and showed a dose-dependent anti-HepG2 effect, not by causing apoptosis or necrosis but by inducing ROS accumulation, leading to inhibition of cell proliferation. The data indicate the potential application of LE-derived antitumor peptide as a complementary agent for human hepatoma treatment.

摘要

旋毛虫是一种组织寄生的蠕虫,通过摄入含有寄生虫感染性幼虫的未煮熟的肉而引起人类旋毛虫病。然而,已经有文献记录了感染旋毛虫的益处:减少过敏性疾病、抑制胶原诱导性关节炎、延缓 1 型糖尿病的进展、抑制癌细胞增殖。由于传统的癌症治疗方法疗效有限且不可靠,且存在不良反应,因此需要新的辅助治疗剂和策略来提高整体治疗效果。本研究旨在验证感染性幼虫提取物(LE)的抗肿瘤活性,并提取寄生虫衍生的抗肿瘤肽。从感染小鼠横纹肌中收获的旋毛虫感染幼虫的提取物被制备并测试对三种癌细胞系的抗肿瘤活性:肝癌 HepG2、卵巢癌 SK-OV-3 和肺腺癌 A549。结果表明,LE 对 HepG2 细胞的抗肿瘤作用最强。LE 的蛋白质组分析显示了 270 种蛋白质。它们被分类为细胞成分、参与代谢过程的蛋白质和具有多种生物学功能的蛋白质。STRING 分析表明,大多数 LE 蛋白相互连接,在各种代谢过程中发挥关键作用。抗癌肽分析确定了三个候选肽。抗肿瘤肽 2 与 的假设蛋白 T01_4238 匹配,对 HepG2 细胞表现出剂量依赖性的抗作用,不是通过诱导细胞凋亡或坏死,而是通过诱导 ROS 积累,从而抑制细胞增殖。数据表明,LE 衍生的抗肿瘤肽具有作为人类肝癌治疗辅助剂的应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60a1/9086976/7b9a89d86f33/fcimb-12-882608-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60a1/9086976/47cc4bbcb28c/fcimb-12-882608-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60a1/9086976/7b9a89d86f33/fcimb-12-882608-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60a1/9086976/47cc4bbcb28c/fcimb-12-882608-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60a1/9086976/7b9a89d86f33/fcimb-12-882608-g002.jpg

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Trichinella spiralis muscle larvae excretory/secretory products trigger apoptosis and S-phase arrest of the non-small-cell lung cancer line A549.旋毛虫肌幼虫排泄/分泌产物触发非小细胞肺癌细胞系 A549 的细胞凋亡和 S 期阻滞。
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AntiCP 2.0: an updated model for predicting anticancer peptides.
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ERK/MAPK signalling pathway and tumorigenesis.ERK/MAPK信号通路与肿瘤发生
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