研究报告

植物乳植杆菌KSFY01对氧化偶氮甲烷/硫酸葡聚糖钠诱导小鼠炎症相关性结直肠癌的效果及机制研究

  • 余婷 ,
  • 赵欣 ,
  • 胡甜甜
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  • (重庆第二师范学院 儿童营养与健康发展协同创新中心,重庆市功能性食品工程技术研究中心,功能性食品研发重庆市工程实验室,重庆,400067)
第一作者:博士,副研究员(胡甜甜讲师为通信作者,E-mail:hutt@cque.edu.cn)

收稿日期: 2024-09-04

  修回日期: 2024-11-28

  网络出版日期: 2025-09-29

基金资助

重庆市教育委员会科学技术研究计划青年项目资助项目(KJQN202201601);重庆市自然科学基金面上项目(cstc2021jcyj-msxmX0424)

Effects and mechanisms of Lactiplantibacillus plantarum KSFY01 on azoxymethane/dextran sodium sulfate-induced inflammation-associated colorectal cancer in mice

  • YU Ting ,
  • ZHAO Xin ,
  • HU Tiantian
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  • (Collaborative Innovation Center for Child Nutrition and Health Development, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing 400067, China)

Received date: 2024-09-04

  Revised date: 2024-11-28

  Online published: 2025-09-29

摘要

该研究通过氧化偶氮甲烷(azoxymethane,AOM)和硫酸葡聚糖钠(dextran sodium sulfate,DSS)诱导小鼠炎症相关性结直肠癌模型,探究分离自新疆传统发酵酸乳中的植物乳植杆菌KSFY01(Lactiplantibacillus plantarum KSFY01,LP-KSFY01)对实验小鼠的作用效果及机制。实验设置正常组、模型组、阿司匹林组以及LP-KSFY01低、高浓度(1×108、1×109CFU/kg)组,除正常组外,各组小鼠均用AOM/DDS处理,阿司匹林组每日灌胃67 mg/kg阿司匹林,菌组每日灌胃LP-KSFY01菌悬液。实验测定小鼠体重、脏器质量、结直肠长度,统计肠组织肿瘤数,对直肠进行组织病理学分析;利用酶联免疫吸附法检测小鼠血清和结肠中炎症细胞因子含量;实时荧光定量PCR测定结肠中NF-κB和细胞凋亡通路相关因子mRNA表达。实验结果显示LP-KSFY01干预能显著缓解体重减轻和脏器指数异常,减少肠道肿瘤发生率,改善肠道组织病理学损伤,降低血清和结肠中IL-6、IL-1β、TNF-α、核因子κB(nuclear factor κB,NF-κB)和诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)等炎症细胞因子含量,下调结肠中IκBβ、p65、p50、p52、Bcl-2和Bcl-xL基因的表达水平,提高Bid和caspase-8基因的表达水平(P<0.05),且高浓度的LP-KSFY01效果优于低浓度。综上,LP-KSFY01可通过调节NF-κB和细胞凋亡途径,发挥缓解肠道炎症进程和干预肠道肿瘤发展的作用,表明LP-KSFY01对小鼠炎症相关性结直肠癌具有潜在的调节作用,有进一步研究的价值。

本文引用格式

余婷 , 赵欣 , 胡甜甜 . 植物乳植杆菌KSFY01对氧化偶氮甲烷/硫酸葡聚糖钠诱导小鼠炎症相关性结直肠癌的效果及机制研究[J]. 食品与发酵工业, 2025 , 51(17) : 108 -117 . DOI: 10.13995/j.cnki.11-1802/ts.040958

Abstract

A mouse model of inflammation-related colorectal cancer was established through the induction of azoxymethane (AOM) and dextran sodium sulfate (DSS) to investigate the effects and mechanisms of Lactiplantibacillus plantarum KSFY01 (LP-KSFY01), isolated from traditional fermented yogurt in Xinjiang.The experimental design included a normal group, a model group, an aspirin group, as well as groups treated with low (1×108 CFU/kg) and high (1×109 CFU/kg) concentrations of LP-KSFY01.Except for the normal group, all mice underwent treatment with AOM/DSS.The aspirin group received daily oral doses of 67 mg/kg of aspirin, while the LP-KSFY01 groups were administered daily oral suspensions of LP-KSFY01.Measurements were taken of body weight, organ weight, colon length, and the number of intestinal tumors, along with histopathological analyses of the rectum.Enzyme-linked immunosorbent assay was utilized to assess the levels of inflammatory cytokines in serum and colon tissues, and real-time fluorescence quantitative PCR was employed to measure the mRNA expression of NF-κB and apoptosis-related factors in the colon.Results indicated that LP-KSFY01 intervention significantly mitigated weight loss and normalized organ indices, reduced the incidence of intestinal tumors, and improved histopathological damage in the rectum.Furthermore, a decrease in the levels of inflammatory cytokines such as IL-6, IL-1β, TNF-α, and iNOS was observed in both serum and colon tissues (P<0.05).The mRNA expression of IκBβ, p65, p50, p52, Bcl-2, and Bcl-xL was downregulated, while the expression of Bid and caspase-8 was upregulated (P<0.05).Notably, a greater effect was noted with the high concentration of LP-KSFY01 compared to the low concentration.In conclusion, LP-KSFY01 may play a role in alleviating intestinal inflammation progression, intervening in colorectal tumor development through modulating the NF-κB and apoptosis pathways, indicating a potential regulatory effect on inflammation-related colorectal cancer in mice and suggesting further research value.

参考文献

[1] SUNG H, FERLAY J, SIEGEL R L, et al.Global cancer statistics 2020:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA:A Cancer Journal for Clinicians, 2021, 71(3):209-249.
[2] THANIKACHALAM K, KHAN G.Colorectal cancer and nutrition[J].Nutrients, 2019, 11(1):164.
[3] PANG Y J, KARTSONAKI C, GUO Y, et al.Adiposity and risks of colorectal and small intestine cancer in Chinese adults:A prospective study of 0.5 million people[J].British Journal of Cancer, 2018, 119(2):248-250.
[4] AXELRAD J E, LICHTIGER S, YAJNIK V.Inflammatory bowel disease and cancer:The role of inflammation, immunosuppression, and cancer treatment[J].World Journal of Gastroenterology, 2016, 22(20):4794-4801.
[5] CLARK C R, STARR T K.Mouse models for the discovery of colorectal cancer driver genes[J].World Journal of Gastroenterology, 2016, 22(2):815-822.
[6] PARANG B, BARRETT C W, WILLIAMS C S.AOM/DSS model of colitis-associated cancer[J].Methods in Molecular Biology, 2016, 1422:297-307.
[7] EICHELE D D, KHARBANDA K K.Dextran sodium sulfate colitis murine model:An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis[J].World Journal of Gastroenterology, 2017, 23(33):6016-6029.
[8] MARTIN M, SUN M Y, MOTOLANI A, et al.The pivotal player:Components of NF-κB pathway as promising biomarkers in colorectal cancer[J].International Journal of Molecular Sciences, 2021, 22(14):7429.
[9] HU R T, CHANTANA W, PITCHAKARN P, et al.Ficus dubia latex extract induces cell cycle arrest and apoptosis by regulating the NF-κB pathway in inflammatory human colorectal cancer cell lines[J].Cancers, 2022, 14(11):2665.
[10] WANG S, LIU Z J, WANG L S, et al.NF-κB signaling pathway, inflammation and colorectal cancer[J].Cellular & Molecular Immunology, 2009, 6(5):327-334.
[11] DUAN B J, ZHAO Y N, BAI J, et al.Colorectal cancer:An overview[M].Gastrointestinal Cancers.Brisbane:Exon Publications, 2022.
[12] BOSETTI C, SANTUCCI C, GALLUS S, et al.Aspirin and the risk of colorectal and other digestive tract cancers:An updated meta-analysis through 2019[J].Annals of Oncology, 2020, 31(5):558-568.
[13] DREW D A, CAO Y, CHAN A T.Aspirin and colorectal cancer:The promise of precision chemoprevention[J].Nature Reviews Cancer, 2016, 16(3):173-186.
[14] LI Z Y, WANG Z, SHEN B L, et al.Effects of aspirin on the gastrointestinal tract:Pros vs.cons[J].Oncology Letters, 2020, 20(3):2567-2578.
[15] 刘利军, 张晓桐, 靳奇文, 等.益生菌对结直肠癌的改善作用与机制的研究进展[J].食品工业科技, 2022, 43(21):405-413.
LIU L J, ZHANG X T, JIN Q W, et al.Research progress on the improvement effect and mechanism of probiotics on colorectal cancer[J].Science and Technology of Food Industry, 2022, 43(21):405-413.
[16] 陈欢. 新疆哈萨克族传统奶酪中乳酸菌发酵剂的筛选及对奶酪风味影响的研究[D].石河子:石河子大学, 2019.
CHEN H.Screening of lactic acid bacteria starter in Xinjiang Kazakh traditional cheese and its effect on cheese flavor[D].Shihezi:Shihezi University, 2019.
[17] GARCIA-GONZALEZ N, BATTISTA N, PRETE R, et al.Health-promoting role of Lactiplantibacillus plantarum isolated from fermented foods[J].Microorganisms, 2021, 9(2):349.
[18] JAVID H, ORYANI M A, AKBARI S, et al.L.plantarum and L.lactis as a promising agent in treatment of inflammatory bowel disease and colorectal cancer[J].Future Microbiology, 2023, 18:1197-1209.
[19] LIU Z H, ZHANG P, MA Y L, et al.Lactobacillus plantarum prevents the development of colitis in IL-10-deficient mouse by reducing the intestinal permeability[J].Molecular Biology Reports, 2011, 38(2):1353-1361.
[20] SCHULTZ M, VELTKAMP C, DIELEMAN L A, et al.Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice[J].Inflammatory Bowel Diseases, 2002, 8(2):71-80.
[21] 黄学红, 王领, 倪敏.植物乳杆菌对结直肠癌作用及机制的研究进展[J].甘肃医药, 2023, 42(1):7-10.
HUANG X H, WANG L, NI M.Research progress on the effect and mechanism of Lactobacillus plantarum on colorectal cancer[J].Gansu Medical Journal, 2023, 42(1):7-10.
[22] AN J, HA E M.Combination therapy of Lactobacillus plantarum supernatant and 5-fluouracil increases chemosensitivity in colorectal cancer cells[J].Journal of Microbiology and Biotechnology, 2016, 26(8):1490-1503.
[23] LI C, SI J, TAN F, et al.Lactobacillus plantarum KSFY06 prevents inflammatory response and oxidative stress in acute liver injury induced by D-Gal/LPS in mice[J].Drug Design, Development and Therapy, 2021, 15:37-50.
[24] DE ROBERTIS M, MASSI E, POETA M L, et al.The AOM/DSS murine model for the study of colon carcinogenesis:From pathways to diagnosis and therapy studies[J].Journal of Carcinogenesis, 2011, 10:9.
[25] MICHAEL B, YANO B, SELLERS R S, et al.Evaluation of organ weights for rodent and non-rodent toxicity studies:A review of regulatory guidelines and a survey of current practices[J].Toxicologic Pathology, 2007, 35(5):742-750.
[26] 田小芸, 恽时锋, 周森妹, 等.C57BL/KsJ-db/db,+/db小鼠主要脏器重量及脏器系数的测定[J].中国比较医学杂志, 2006, 16(4):220-222.
TIAN X Y, YUN S F, ZHOU S M, et al.The weight of main organs and organ coefficient in db/db and +/db mice[J].Chinese Journal of Comparative Medicine, 2006, 16(4):220-222.
[27] MIN J K, LEE C H, JANG S E, et al.Amelioration of trinitrobenzene sulfonic acid-induced colitis in mice by liquiritigenin[J].Journal of Gastroenterology and Hepatology, 2015, 30(5):858-865.
[28] BISSAHOYO A, PEARSALL R S, HANLON K, et al.Azoxymethane is a genetic background-dependent colorectal tumor initiator and promoter in mice:Effects of dose, route, and diet[J].Toxicological Sciences, 2005, 88(2):340-345.
[29] ERBEN U, LODDENKEMPER C, DOERFEL K, et al.A guide to histomorphological evaluation of intestinal inflammation in mouse models[J].International Journal of Clinical and Experimental Pathology, 2014, 7(8):4557-4576.
[30] ZHAO H K, WU L, YAN G F, et al.Inflammation and tumor progression:Signaling pathways and targeted intervention[J].Signal Transduction and Targeted Therapy, 2021, 6:263.
[31] 李文彬. 炎症因子和益生菌在溃疡性结肠炎癌变中的作用与相关机制研究[D].北京:北京协和医学院, 2017.
LI W B.The role and mechanism of inflammatory factors and probiotics in the carcinogenesis of ulcerative colitis[D].Beijing:Peking Union Medical College, 2017.
[32] OSHIMA H, OSHIMA M.The inflammatory network in the gastrointestinal tumor microenvironment:Lessons from mouse models[J].Journal of Gastroenterology, 2012, 47(2):97-106.
[33] 曾心雨. 双歧杆菌制剂对ERAS路径下老年结直肠癌患者术后恢复的影响研究[D].湖南:湖南师范大学, 2022.
ZENG X Y.Study on the effect of Bifidobacterium preparationon postoperative recovery of elderly patients with colorectal cancer under ERAS pathway[D].Hunan:Hunan Normal University, 2022.
[34] LOPETUSO L R, CHOWDHRY S, PIZARRO T T.Opposing functions of classic and novel IL-1 family members in gut health and disease[J].Frontiers in Immunology, 2013, 4:181.
[35] 贾前生, 左锋.植物乳杆菌L15对过度运动引起大鼠骨骼肌损伤的改善作用[J].食品科学, 2023, 44(13):79-87.
JIA Q S, ZUO F.Ameliorative effect of Lactobacillus plantarum L15 on excessive exercise-induced skeletal muscle injury in rats[J].Food Science, 2023, 44(13):79-87.
[36] WANG Y J, PASZEK P, HORTON C A, et al.A systematic survey of the response of a model NF-κB signalling pathway to TNFα stimulation[J].Journal of Theoretical Biology, 2012, 297(2-12):137-147.
[37] 师鑫鹏, 罗晓勇, 李朝萍, 等.西妥昔单抗联合化疗治疗对耐药晚期结直肠癌患者近期疗效及血清NF-κB、EGFR、HER-2水平的影响[J].实用中西医结合临床, 2021, 21(19):92-93.
SHI X P, LUO X Y, LI C P, et al.Short-term effect of cetuximab combined with chemotherapy on patients with drug-resistant advanced colorectal cancer and its influence on serum NF-κB, EGFR and HER-2 levels[J].Practical Clinical Journal of Integrated Traditional Chinese and Western Medicine, 2021, 21(19):92-93.
[38] 杨晓东, 王杉, 于永祥, 等.细胞核因子NFkB在人大肠癌组织中的表达及意义[J].中华普通外科杂志, 2000, 15(6):367-369.
YANG X D, WANG S, YU Y X, et al.Expression of nuclear factor-kB(NF-kB) in human colorectal cancer[J].Chinese Journal of General Surgery, 2000, 15(6):367-369.
[39] WANG H, WANG L Y, XIE Z X, et al.Nitric oxide (NO) and NO synthases (NOS)-based targeted therapy for colon cancer[J].Cancers, 2020, 12(7):1881.
[40] WEI H, PRABHU L, HARTLEY A V, et al.Methylation of NF-κB and its role in gene regulation[M].Gene Expression and Regulation in Mammalian Cells- Transcription From General Aspects.Rijeka:InTech, 2018
[41] THOMS H C, STARK L A.The NF-κB nucleolar stress response pathway[J].Biomedicines, 2021, 9(9):1082.
[42] KAMATA H, TSUCHIYA Y, ASANO T.IκBβ is a positive and negative regulator of NF-κB activity during inflammation[J].Cell Research, 2010, 20(11):1178-1180.
[43] MALEK S, HUANG D B, HUXFORD T, et al.X-ray crystal structure of an IkappaBbeta x NF-kappaB p65 homodimer complex[J].Journal of Biological Chemistry, 2003, 278(25):23094-23100.
[44] TAKEUCHI O, AKIRA S.Pattern recognition receptors and inflammation[J].Cell, 2010, 140(6):805-820.
[45] HUANG G L, CHEN X J, CAI Y F, et al.miR-20a-directed regulation of BID is associated with the TRAIL sensitivity in colorectal cancer[J].Oncology Reports, 2017, 37(1):571-578.
[46] AMIN M, NAVIDIFAR T, SAEB S, et al.Tumor-targeted induction of intrinsic apoptosis in colon cancer cells by Lactobacillus plantarum and Lactobacillus rhamnosus strains[J].Molecular Biology Reports, 2023, 50(6):5345-5354.
[47] TUMMERS B, GREEN D R.Caspase-8:Regulating life and death[J].Immunological Reviews, 2017, 277(1):76-89.
[48] SUN M Y, LIU W W, SONG Y L, et al.The effects of Lactobacillus plantarum-12 crude exopolysaccharides on the cell proliferation and apoptosis of human colon cancer (HT-29) cells[J].Probiotics and Antimicrobial Proteins, 2021, 13(2):413-421.
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