lncRNA NKILA促进结直肠腺癌细胞的增殖和侵袭

目的:探讨lncRNA NKILA对结直肠腺癌细胞增殖和侵袭的影响。方法:对结直肠腺癌病人的肿瘤组织和癌旁组织进行lncRNA测序分析,以肿瘤组织表达明显增高的lncRNA NKILA作为研究对象。将结直肠腺癌细胞DLD-1分为3组,即未转染慢病毒的空白对照组,转染无序序列慢病毒的阴性对照组,以及转染沉默lncRNA NKILA序列的试验组。流式细胞术检测转染效率,qRT-PCR检测lncRNA表达。CCK-8实验和Transwell实验分别检测DLD-1细胞的增殖和侵袭。将三组细胞分别皮下注射到小鼠体内构建荷瘤小鼠模型,观察移植瘤体积以及生存时间。Western blot检测lncRNA NKILA对DLD-1细胞中NF-κB信号通路的影响。结果:相比癌旁组织,结直肠癌组织中的lncRNA NKILA表达显著增高。通过转染慢病毒,试验组DLD-1细胞中lncRNA NKILA表达明显降低（P＜0.01）。CCK-8检测结果显示,相比阴性对照组,试验组增殖率降低（P＜0.05）。Transwell实验结果显示,相比阴性对照组,试验组DLD-1细胞侵袭能力明显降低（P＜0.01）。试验组小鼠肿瘤体积较阴性对照组减小（P＜0.05或P＜0.001）,生存时间明显延长（中位生存期75 vs 58 d,P＜0.05）。lncRNA NKILA可以抑制IκBα的磷酸化和p65的核转位。结论:lncRNA NKILA可以促进结直肠腺癌细胞DLD-1的增殖和侵袭,这种作用与lncRNA NKILA抑制NF-κB信号通路相关。     

阿克曼菌对AOM/DSS炎症相关性结直肠癌发生的作用

目的 探讨阿克曼菌（AKK）对氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导的炎症相关性结直肠癌小鼠模型及其肠道干细胞的影响。方法 AOM/DSS诱导小鼠炎症相关性结直肠癌模型随机分为三组,通过灌胃方式给予三组不同的药物分别为模型组（Model）、AKK组及阿司匹林组（Aspirin）。干预10周后观察小鼠的肿瘤数目、肿瘤大小、肿瘤分布及分析肿瘤负荷情况。免疫组织化学分析表征肿瘤恶性化的蛋白Ki67和表征干细胞的特异性蛋白Lgr5的表达变化。qRT-PCR检测干细胞分化特性的基因Lgr5、CD133、Nanog和ALDH1的mRNA表达。结果 与模型组相比,AKK组的肿瘤数目、肿瘤大小及肿瘤负荷明显减小（P<0.01）;相较于模型组小鼠,AKK组的肿瘤组织中Ki67和Lgr5表达明显下降（P<0.05）;CD133、Nanog和ALDH1的mRNA表达明显下调。结论 AKK对AOM/DSS诱导的结肠炎相关性结直肠癌小鼠具有防治作用,其作用机制可能与结直肠干细胞活性密切相关。     

芥菜籽对氧化偶氮甲烷诱导小鼠结直肠癌的影响

背景与目的:结直肠癌是常见的恶性肿瘤之一,在我国发病率和死亡率呈不断上升趋势.文献报道芥菜籽具有抗肿瘤的活性,本研究旨在观察在氧化偶氮甲烷(azoxymethane,AOM)诱发昆明种小鼠发生结直肠癌的过程中,通过芥菜籽(mustard seed,MS)进行饮食干预能否预防肿瘤的发生.方法:选择6周龄昆明种雌性小鼠,随机分为AOM组、AOM+5%MS干预组、AOM+10%MS干预组和正常对照组.小鼠皮下注射AOM(10 mg/kg体质量),每周1次,连续3周.32周时颈椎脱臼处死小鼠,分离结直肠,用预冷的0.9%NaCl溶液冲洗肠内容物.观察记录各组小鼠有无肿瘤发生及发生数目、大小和位置,计算肿瘤发生率.结果:正常对照组小鼠未发现肿瘤,AOM模型组小鼠结直肠肿瘤发生率为86.7%,5%MS干预组及10%MS干预组小鼠结直肠肿瘤发生率分别为60.0%和41.7%,与模型组相比差异均有统计学意义(P＜0.05).AOM模型组小鼠荷瘤数为(2.2±1.2)个,而5%MS干预组和10%MS干预组小鼠荷瘤数分别为(1.1±1.1)个和(0.7±0.9)个,与AOM模型组相比差异均有统计学意义(P＜0.05).结论:通过芥菜籽饮食干预能够抑制UAOM诱导的小鼠结直肠癌的发生发展,可进一步用于结直肠癌防治的研究.     

核因子-κB、血管内皮生长因子在肾癌中的表达及其与预后的关系

 目的　研究核因子-κB（NF-κB）和血管内皮生长因子（VEGF）在肾癌中的表达及其与患者预后的关系。方法　应用免疫组织化学方法（EnVision二步法）检测40份肾癌组织及10份正常肾组织中的NF-κB p65和VEGF的表达,并结合肾癌患者的预后进行分析。结果　NF-κB p65在肾癌组织中显著表达（65.0 %）,正常肾组织中呈阴性表达;VEGF在肾癌中表达率为67.5 ％,显著高于正常肾组织中 的表达率（20.0 %,P＜0.05）;肾癌中NF-κB p65的表达与VEGF的表达呈正相关（r＝0.498,P＜0.01）;NF-κB p65表达阳性组5年生存率明显低于阴性组（P＜0.05）;VEGF表达阳性组5年生存率明显低于阴性组（P＜0.05）;NF-κB p65、VEGF双阳性组的5年生存率明显低于双阴性组（P＜0.01）。结论　NF-κB在肾癌中呈异常活性表达,其可能通过多种途径参与肾癌的发生、发展;NF-κB对于VEGF的高表达可能具有潜在的正向调节作用。NF-κB、VEGF在肾癌组织中的表达对于患者的预后具有一定意义。     

G-CSF在结肠炎相关结直肠癌中的表达

目的 探索粒细胞集落刺激因子(granulocyte-colony stimulating factor,G-CSF)在结肠炎相关结直肠癌小鼠模型中的表达情况,并研究小鼠结直肠部位G-CSF的细胞来源.方法 利用致癌剂氧化偶氮甲烷(azoxy-methane,AOM)和致炎剂葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导小鼠的结直肠癌,通过免疫组化方法 检测G-CSF在炎症向肿瘤发展各阶段小鼠结直肠组织中的表达情况,利用免疫荧光方法 检测小鼠结直肠部位与G-CSF共定位的细胞.结果 AOM/DSS小鼠模型能良好地模拟结肠炎相关结直肠癌病程特点:本研究将其分为3个阶段,即AD1、AD2、AD3阶段.其中AD1阶段小鼠结直肠部位存在大量淋巴细胞的浸润,AD2阶段小鼠有不典型增生和腺瘤,AD3阶段小鼠结直肠出现原位癌病变.与正常小鼠相比,AD1、AD2、AD3阶段小鼠结直肠部位G-CSF表达升高,且AD2阶段表达水平最高;G-CSF与小鼠结直肠部位的上皮细胞共定位最广泛,只有少量的肌成纤维细胞和巨噬细胞能跟G-CSF共定位.结论 本研究中AOM/DSS小鼠模型经历了正常黏膜→不典型增生→腺瘤→腺癌的发展过程,能够较好地模拟人由炎症性肠病逐步发展成结肠炎相关结直肠癌的病程;AD小鼠与正常小鼠相比表达较高水平的G-CSF,且AD2阶段G-CSF表达最高;AOM/DSS小鼠模型中,G-CSF主要由小鼠结直肠部位的上皮细胞分泌,部分巨噬细胞和肌成纤维细胞也可以产生G-CSF.     

乳腺癌中核转录因子-κB p50表达及其与细胞凋亡的关系

 目的 研究核转录因子-κB p50 （NF-κB p50）在乳腺癌组织中的表达和意义及其与细胞凋亡的关系。方法 应用Elivision免疫组化染色法和脱氧脱氧核糖核酸末端转移酶介导的缺口末端标记（TUNEL）技术，对65例乳腺癌组织中NF-κB p50、凋亡细胞表达进行原位观察和比较,并结合临床资料进行分析。结果 65例乳腺癌标本NF-κB p50表达阳性率为70.8 %（46／65），细胞凋亡指数（AI）为（4.59±1.94）%； NF-κB p50表达强度与患者的肿瘤的大小、组织分级、孕激素受体（PR）无关（P＞0.05）；与腋淋巴结转移数、雌激素受体（ER）状况明显相关（P＜0.05）。NF-κB p50表达阴性的乳腺癌中AI明显高于NF-κB p50 表达阳性组（P＜0.05）。NF-κB p50活性强度与AI呈明显的负相关（P＜0.001）。结论 NF-κB p50的异常激活在早期乳腺癌的发生和转化中起重要作用，其抑制凋亡活性与肿瘤侵袭转移及恶性潜能密切相关，对NF-κB p50活性及细胞凋亡的检测有助于乳腺癌的临床分析，并有望成为预后的观察指标。     

吴茱萸碱对急性放射性肠炎肠黏膜的保护作用及机制

目的:探讨吴茱萸碱对急性放射性肠炎疗效及对肠黏膜屏障保护的机制。方法:清洁级小鼠50只,随机分为正常组、模型组、吴茱萸碱预防加治疗组（简称预治组）、吴茱萸碱治疗组（简称治疗组）、思密达组。预治组提前灌胃给药1周。除正常组外的各组采用高能Ｘ射线照射,总剂量6Gy,建立急性放射性肠炎模型。照射后12ｈ连续灌胃给药1周。光学显微镜下观察及图像分析软件测定其相关形态学指标,并免疫组化法测定肠组织NF-κB p65蛋白活性,ELISA法测定肿瘤坏死因子α（TNF-α）含量。结果:各给药组小鼠肠组织隐窝深度、黏膜及全层壁厚度均显著高于模型组（P＜0.01）。NF-κB p65蛋白表达（P＜0.01）、TNF-α含量（P＜0.01）显著低于模型组。预治组好于治疗组和思密达组,差异有统计学意义（P＜0.05）。治疗组与思、密达组比较差异没有统计学意义（P＞0.05）。结论:吴茱萸碱可明显升高放射性肠炎肠组织隐窝深度、黏膜及全层壁厚度,降低其NF-κB p65蛋白表达,降低TNF-α含量。吴茱萸碱上述作用与给药时机和时间相关,放射治疗前即开始预防性用药比单纯治疗给药保护肠黏膜的作用更强。     

芥菜籽预防化学诱导小鼠大肠肿瘤的实验研究

目的 评价芥菜籽（MS）对氧化偶氮甲烷（AOM）诱导的小鼠大肠肿瘤的预防作用及其机制。方法 选择60只昆明种小鼠,随机均分为AOM 模型组、AOM+5％MS干预组、AOM+10％MS干预组和正常对照组（生理盐水）。记录各组小鼠有无肿瘤发生及发生数目、大小和位置, 计算平均肿瘤数和肿瘤发生率;HE染色确定肿瘤的组织学类型;免疫组化染色检测肿瘤组织中PCNA蛋白的表达,计算增殖指数（PI）;TUNEL染色检测肿瘤组织凋亡情况,计算凋亡指数（AI）。结果 正常对照组小鼠无肿瘤发生,AOM模型组、5％MS干预组和10％MS干预组小鼠肿瘤发生率分别为86.7％、 60.0％、41.7％,组间差异有统计学意义（P=0.048）; 5％MS干预组平均肿瘤数为1.07±1.10,10％MS干预组为0.67±0.89,均较AOM模型组的2.20±1.21少（P＜0.05）;10％MS干预组PI为32.0±3.9,均低于AOM模型组和5％MS干预组的59.9±4.4和41.7±4.9（P＜0.05）;10％MS干预组AI为15.0±2.4,均高于AOM模型组和5％MS干预组的6.9±1.4和9.3±1.5（P＜0.05）。结论 MS对AOM诱导的小鼠大肠肿瘤具有化学预防作用,其机制为抑制肿瘤细胞增殖和诱导肿瘤细胞凋亡。     

紫杉醇节律化疗抗Lewis肺癌血管生成作用的实验研究

目的 观察紫杉醇节律化疗对C57BL/6小鼠Lewis肺癌(LLC)肿瘤生长及血管生成的影响并探讨其可能的机制.方法 建立小鼠LLC模型,随机分组后分别给予紫杉醇节律化疗和生理盐水腹腔注射,隔天测量小鼠体重及肿瘤体积.小鼠处死后称瘤重,应用免疫组化观察小鼠肿瘤组织中微血管和巨噬细胞、NF-κB蛋白的表达.结果 节律化疗组小鼠移植瘤的生长速度减慢,对照组皮下瘤重及体积明显大于节律化疗组(P＜0.05),节律化疗组微血管和巨噬细胞减少(P＜0.05),NF-κB蛋白表达亦减少(P＜0.05).巨噬细胞计数与微血管计数有相关关系.结论 紫杉醇节律化疗可明显抑制小鼠LLC的生长及血管生成,其可能机制之一是节律化疗可以下调小鼠肿瘤组织中的NF-κB蛋白表达,从而减少肿瘤新生血管生成.     

CTSB在肝内胆管细胞癌中表达及对癌细胞增殖及NF-κB信号通路的影响

摘 要：［目的］探讨人组织蛋白酶B（CTSB）在肝内胆管细胞癌中表达及对癌细胞增殖及核因子-κB（NF-κB）信号通路的影响。［方法］ 采用Western blot检测肝内胆管癌细胞中CTSB蛋白表达,使用siRNA对CTSB沉默后采用Edu实验检测细胞增殖,同时检测NF-κB信号通路中相应蛋白表达情况。［结果］与正常肝细胞系相比,肝内胆管癌细胞RBE、HCCC9810、HUCCT1中CTSB蛋白表达水平均明显提高（t=7.724、8.839、7.983,P=0.002、0.001、0.002）。与Control组相比,CTSB-siRNA组的CTSB蛋白表达量明显下降（t=6.131,P=0.004）,细胞增殖比例明显下降（t=5.271,P=0.006）,且CTSB-siRNA组的NF-κB抑制蛋白α（IκB-α）、IκB激酶β（IKK-β）、IKKα和p-NF-κB蛋白水平明显下降（t=6.069、5.433、6.365、5.717,P=0.004、0.006、0.003、0.005）。［结论］ 肝内胆管细胞癌中CTSB蛋白表达水平明显上调,且CTSB能够通过活化NF-κB信号通路促进肿瘤细胞增殖。     

YYFZBJS inhibits colorectal tumorigenesis by remodeling gut microbiota and influence on M2 macrophage polarization in vivo and in vitro

Our previous studies indicated that the extract of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) had potent anticancer activities by significantly inhibiting intestinal tumor development in Apc^Min/+ mice. However, knowledge regarding the mechanism and effect of YYFZBJS in the prevention of colorectal cancer is limited. In this study, we aim to investigate the preventive effects of YYFZBJS in enterotoxigenic Bacteroides fragilis (ETBF)-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis. First, the colonic tissues of the AOM/DSS mouse models were collected for biomedical analysis, and gut microbiota profiling was detected post YYFZBJS treatment using a 16S rRNA gene sequencing. Then, antibiotic solution (Abx) mice were acclimated with AOM/DSS treatment and then fed with ETBF with or without YYFZBJS for three cycles. As expected, the intragastric administration of YYFZBJS in the AOM/DSS mouse model significantly decreased the tumor load, the severity of disease activity index (DAI) scores, and the level of M2 macrophage markers such as CD206, Arg-1 and IL-10. Notably, the reverse of polarized macrophages induced by YYFZBJS could suppress CRC cell proliferation and infiltration, as demonstrated by the decrease of some tumor proliferation-related proteins in a dose-dependent manner. Importantly, ETBF dysbiosis can contribute to colon tumor development by stimulating p-STAT3 mediated M2 macrophages polarization to promote chronic inflammation and adenoma malignant transformation, which YYFZBJS can effectively limit. Altogether, we demonstrate that ETBF dysbiosis may contribute to M2 macrophages-promoted colon carcinogenesis and progression of CRC cells, while YYFZBJS could be a promising protective agent against ETBF-mediated colorectal cancer.     

阿司匹林对结肠炎相关结直肠癌小鼠模型肿瘤细胞凋亡的影响

目的探讨阿司匹林对结肠炎相关结直肠癌（CAC）小鼠模型的肿瘤形成、肿瘤细胞凋亡以及肠道炎症的影响。方法 将60只雄性Balb／c小鼠随机分为模     

Metformin inhibited colitis and colitis-associated cancer (CAC) through protecting mitochondrial structures of colorectal epithelial cells in mice

Although a mountain of papers have showed that metformin plays a role in inhibiting cancers, but the mechanism underpinning this has not yet fully elucidated. Herein, we used AOM/DSS model, the clinicopathological features are similar to those found in humans, to investigate the effects of metformin as well as combination with 5-FU in the prevention of colitis and colitis associated cancer (CAC). Oral metformin significantly inhibited DSS-induced ulcerative colitis and AOM/DSS-induced CAC. Metformin also ameliorated 5-FU-induced colorectal gastrointestinal symptoms in mice. Metformin combination with 5-FU strongly inhibited colorectal cancer. Metformin reduced levels of the NFκB signaling components p-IKKα/β, p-NFκB, p-IκBα in colorectal mucosal cells. Transmission electron microscopy analysis suggested that the inhibition of metformin on colitis and CAC might associate with its biological activity of protecting mitochondrial structures of colorectal epithelial cells. Further analysis by Mito Tracker Red staining assay indicated that metformin prevented H₂O₂-induced mitochondrial fission correlated with a decrease of mitochondrial perimeter. In addition, metformin increased the level of NDUFA9, a Q-module subunit required for complex I assembly, in colorectal epithelial cells. These observations of metformin in the inhibition of colitis and CAC might associate with its activity of activating the LKB1/AMPK pathway in colorectal epithelial cells. In conclusion, metformin inhibited colitis and CAC through protecting the mitochondrial structures of colorectal epithelial cells.     

Estrogen receptor-β protects against colitis-associated neoplasia in mice

Estrogen receptor-beta (ERβ) has been suggested to exert anti-inflammatory and anti-tumorigenic effects in the colon, providing a translational potential to prevent and/or treat inflammatory bowel disease (IBD) and its progression to colitis-associated colorectal cancer (CAC). However, the specific direct role of ERβ in CAC has not yet been tested. We assessed the effects of ERβ deficiency in the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CAC model using ERβ knockout (βERKO) mice and wild-type (WT) littermates. These mice were injected with AOM followed by 1 week of DSS treatment, and sacrificed on weeks 9 or 16. βERKO mice developed more severe clinical colitis compared to WT mice, as evidenced by significantly higher disease activity index after DSS treatment, weight to length ratio of the colons, inflammation score and grade of dysplasia. ERβ-deficient colons presented greater number and size of polyps at weeks 9 and 16, respectively, and were characterized by a significant increase in interleukin (IL)-6, IL-17, tumor necrosis factor alpha and interferon-gamma mRNA levels. Furthermore, higher protein expression levels of nuclear factor-kappa B, inducible nitric oxide synthase, β-catenin, proliferating cell nuclear antigen, mucin-1 and significantly lower caveolin-1 and mucin-2 protein levels were shown in βERKO mice compared to WT mice. These data suggest a possible anti-inflammatory and anti-neoplastic mechanism of action of ERβ in CAC. These results demonstrate for the first time that ERβ provides protection in the AOM/DSS-induced CAC model in mice, suggesting a preventive and/or therapeutic potential for the use of ERβ-selective agonists in IBD.     

Blockade of MK2 is protective in inflammation‐associated colorectal cancer development

Chronic inflammation is a risk factor for colorectal cancer. The MAPK‐activated protein kinase 2 (MK2) pathway controls multiple cellular processes including p38‐dependent inflammation. This is the first study to investigate the role of MK2 in development of colitis‐associated colon cancer (CAC). Herein, we demonstrate that MK2^?/? mice are highly resistant to neoplasm development when exposed to AOM/DSS, while wild type (WT) C57BL/6 develop multiple neoplasms with the same treatment. MK2‐specific cytokines IL‐1, IL‐6 and TNF‐α were substantially decreased in AOM/DSS treated MK2^?/? mouse colon tissues compared with WT mice, which coincided with a marked decrease in macrophage influx. Restoring MK2‐competent macrophages by injecting WT bone marrow derived macrophages into MK2^?/? mice led to partial restoration of inflammatory cytokine production with AOM/DSS treatment; however, macrophages were not sufficient to induce neoplasm development. These results indicate that MK2 functions as an inflammatory regulator to promote colonic neoplasm development and may be a potential target for CAC.     

Eicosapentaenoic acid free fatty acid prevents and suppresses colonic neoplasia in colitis‐associated colorectal cancer acting on Notch signaling and gut microbiota

Inflammatory bowel diseases are associated with increased risk of developing colitis‐associated colorectal cancer (CAC). Epidemiological data show that the consumption of ω‐3 polyunsaturated fatty acids (ω‐3 PUFAs) decreases the risk of sporadic colorectal cancer (CRC). Importantly, recent data have shown that eicosapentaenoic acid‐free fatty acid (EPA‐FFA) reduces polyp formation and growth in models of familial adenomatous polyposis. However, the effects of dietary EPA‐FFA are unknown in CAC. We tested the effectiveness of substituting EPA‐FFA, for other dietary fats, in preventing inflammation and cancer in the AOM‐DSS model of CAC. The AOM‐DSS protocols were designed to evaluate the effect of EPA‐FFA on both initiation and promotion of carcinogenesis. We found that EPA‐FFA diet strongly decreased tumor multiplicity, incidence and maximum tumor size in the promotion and initiation arms. Moreover EPA–FFA, in particular in the initiation arm, led to reduced cell proliferation and nuclear β‐catenin expression, whilst it increased apoptosis. In both arms, EPA‐FFA treatment led to increased membrane switch from ω‐6 to ω‐3 PUFAs and a concomitant reduction in PGE₂ production. We observed no significant changes in intestinal inflammation between EPA‐FFA treated arms and AOM‐DSS controls. Importantly, we found that EPA‐FFA treatment restored the loss of Notch signaling found in the AOM‐DSS control and resulted in the enrichment of Lactobacillus species in the gut microbiota. Taken together, our data suggest that EPA‐FFA is an excellent candidate for CRC chemoprevention in CAC.     

TiaochangXiaoliu decoction inhibits azomethane (AOM)/dextran sulfate sodium (DSS)-induced colorectal cancer by regulating immune response

BackgroundTiaochangXiaoliu decoction (TXD) has an anti-tumor effect in clinical practice. We further investigated the role of TXD in colorectal cancer (CRC).MethodsMouse models of CRC were induced by azomethane (AOM)/dextran sulfate sodium (DSS), with sixty male C57BL/6 mice randomly divided into six groups (10 mice/group): a control group, AOM/DSS group, TXD at low dose (L-dose) group, middle dose (M-dose) group, high dose (H-dose) group, and Celecoxib (Cel) group. The colorectum, serum, and plasma of mice in each group was collected following sacrifice to record the number of tumors. HE staining was utilized for observing pathological damage to colorectal tissues, ELISA used for detecting INF-γ, IL-2, and TNF-α expression in serum, and flow cytometry used for measuring the proportion of CD4⁺, CD8⁺, CD4⁺/CD8⁺, and NK cells in plasma.ResultsCompared with the control group, the AOM/DSS group showed tumor masses in the colorectum and different degrees of pathological damage in the intestine. AOM/DSS induction also resulted in an increase in INF-γ, IL-2, and TNF-α expression in serum, and a decrease in the percentages of CD4⁺, CD8⁺, CD4⁺/CD8⁺, and NK cells(P<0.05). In comparison with the AOM/DSS group, with the increase of TXD dose, the number of tumors decreased significantly, and intestinal structure and mucosal inflammatory cell infiltration also improved. Further, in comparison with the AOM/DSS group, all three doses of TXD and celecoxib caused an increase in the contents of CD4⁺, CD8⁺, CD4⁺/CD8⁺, and NK cells in plasma. In addition, in the M-dose, H-dose, and Cel groups, INF-γ, IL-2, and TNF-α expression showed a marked decrease, and the reduction in these two groups treated with TXD was dose-dependent.ConclusionsTXD leads to a marked reduction in the number of tumors and inflammatory cell infiltration in CRC mice. This decoction significantly decreased the levels of INF-γ, IL-2, and TNF-α in serum, and increased the contents of CD4⁺, CD8⁺, CD4⁺/CD8⁺, and NK cell in the plasma of mice with AOM/DSS-induced CRC.