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用于结直肠癌治疗的乳酸菌活性物质及细胞通路的初步研究

Preliminary study on the active substances and cellular pathways of lactic acid bacteria for colorectal cancer treatment.

作者信息

Zhao Si-Hui, Zhang Shu-Ming, Yang Jin-Wei, Liu Chen-Jian, Zeng Xue-Qin, Zhang Yuan-Lian, Chen Si-Qian, Zhao Zhi-Min, Xia Yun-Xin, Li Xiao-Ran, Shang Yun

机构信息

Second Department of General Surgery, First People' s Hospital of Yunnan Province, Kunming 650032, Yunnan, China.

Second Department of General Surgery, Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, Yunnan, China.

出版信息

J Cancer. 2024 Jul 16;15(15):4902-4921. doi: 10.7150/jca.94530. eCollection 2024.

DOI:10.7150/jca.94530
PMID:39132155
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11310875/
Abstract

Colorectal cancer (CRC) is a common malignant tumor and is one of the three most common cancers worldwide. Traditional surgical treatment, supplemented by chemotherapy and radiotherapy, has obvious side effects on patients. Immunotherapy may lead to some unpredictable complications. Low introduction rate and high cost are some of the problems of gene therapy, so finding a safe, reliable and least toxic treatment method became the main research direction for this study. Lactic acid bacteria and their metabolites are widely used in functional foods or as adjuvant therapies for various diseases because they are safe to eat and have no adverse reactions. Research has shown that lactic acid bacteria and their metabolites play an auxiliary therapeutic role in colorectal cancer mainly by improving the intestinal flora composition, inhibiting the growth of pathogenic bacteria and inhibiting the proliferation of cancer cells. It is now widely believed that the substances that probiotics such as lactic acid bacteria exert anti-cancer effects are mainly secondary metabolites such as butyric acid. AY01 isolated from fermented food has good anti-cancer ability, and its main anti-cancer substance is 2'-deoxyinosine. Through flow cytometry detection, it was found that AY01 can block cell proliferation in the S phase. In addition, AY01 culture reduces the sensitivity of mice to colitis-associated CRC induced by azoxymethane (AOM)/dextran sulfate sodium salt (DSS) and exhibits the occurrence and promotion of tumors. According to transcriptome analysis, AY01 may induce apoptosis of colorectal cancer cells by activating the p38 MAPK pathway. This experiment provided possibilities for the treatment of CRC.

摘要

结直肠癌（CRC）是一种常见的恶性肿瘤，是全球三大最常见癌症之一。传统的手术治疗辅以化疗和放疗，对患者有明显的副作用。免疫疗法可能会导致一些不可预测的并发症。基因治疗存在导入率低和成本高的问题，因此寻找一种安全、可靠且毒性最小的治疗方法成为本研究的主要方向。乳酸菌及其代谢产物因其食用安全且无不良反应，被广泛应用于功能性食品或作为各种疾病的辅助治疗方法。研究表明，乳酸菌及其代谢产物在结直肠癌中主要通过改善肠道菌群组成、抑制病原菌生长和抑制癌细胞增殖发挥辅助治疗作用。目前普遍认为，乳酸菌等益生菌发挥抗癌作用的物质主要是丁酸等次生代谢产物。从发酵食品中分离出的AY01具有良好的抗癌能力，其主要抗癌物质是2'-脱氧肌苷。通过流式细胞术检测发现，AY01可在S期阻断细胞增殖。此外，AY01培养物降低了小鼠对由氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导的结肠炎相关结直肠癌的敏感性，并抑制了肿瘤的发生和发展。根据转录组分析，AY01可能通过激活p38 MAPK途径诱导结直肠癌细胞凋亡。该实验为结直肠癌的治疗提供了可能性。

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