研究报告

草黄口蘑多糖对S180荷瘤小鼠抗肿瘤活性分子机制研究

  • 赵倪慧 ,
  • 蒋琳 ,
  • 张丁 ,
  • 段江波 ,
  • 丁祥 ,
  • 侯怡铃
展开
  • 1(西华师范大学 生命科学学院,西南野生动植物资源保护教育部重点实验室,四川 南充,637009)
    2(西华师范大学 环境科学与工程学院,四川 南充,637009)
第一作者:硕士研究生(侯怡铃教授为通信作者,E-mail:starthlh@126.com)

收稿日期: 2023-03-31

  修回日期: 2023-05-22

  网络出版日期: 2024-07-12

基金资助

四川省科技厅应用基础面上项目(2022NSFSC0107);四川省科技厅农业科技成果转化资金项目(2022NZZJ0003);四川省转移支付科技成果转移转化示范项目(22ZYZFSF0009;23ZHSF0082);农业农村部农业微生物资源收集与保藏重点实验室开放课题(KLMRCP2021-01)

Molecular mechanism of anti-tumor activity of polysaccharide from Tricholoma lascivum (Fr.) Gillet on S180 tumor-bearing mice

  • ZHAO Nihui ,
  • JIANG Lin ,
  • ZHANG Ding ,
  • DUAN Jiangbo ,
  • DING Xiang ,
  • HOU Yiling
Expand
  • 1(Key Laboratory of Southwest China Wildlife Resources Conservation (Ministry of Education), College of Life Sciences, China West Normal University, Nanchong 637009, China)
    2(College of Environmental Science and Engineering, China West Normal University, Nanchong 637009, China)

Received date: 2023-03-31

  Revised date: 2023-05-22

  Online published: 2024-07-12

摘要

多糖作为口蘑属真菌的主要功能成分之一,具有免疫调节、抗氧化及抗肿瘤等活性。为明确草黄口蘑多糖的结构特征及其对S180荷瘤小鼠抗肿瘤活性相关分子机制,该研究以草黄口蘑子实体经热水浸提法提取的草黄口蘑多糖[Tricholoma lascivum (Fr.) Gillet polysaccharide,TLG-1]为实验材料,初步解析TLG-1结构,以S180荷瘤小鼠为模型检测体内抗肿瘤活性,并采用转录组测序技术对S180肿瘤组织总RNA进行测序分析。结果表明,TLG-1重均分子质量为13 442 Da,由木糖、甘露糖、葡萄糖和半乳糖4种单糖组成,其比例为1.57∶1.45∶2.84∶4.14。TLG-1可显著抑制荷瘤小鼠S180肿瘤的生长(P<0.01),抑瘤率为53.8%。转录组测序分析显示,TLG-1能显著上调mt-Co1PrlrFoxa1以及下调Pitx2Rplp1Eef1a1Lgals1等基因,影响S180肿瘤细胞的代谢途径,调控细胞周期并抑制上皮间质转化过程。基因本体富集分析表明,TLG-1可激活细胞因子介导的信号通路,引发细胞免疫。京都基因与基因组百科全书富集分析显示,在Jak-STAT信号通路中的Il21Il12rb2Il12bIl2raIl2rbIl2rgIl15raIfng等基因显著上调,通过转换肿瘤相关巨噬细胞表型及分泌干扰素-γ等,增强小鼠抗肿瘤免疫应答。该研究结果为草黄口蘑多糖的开发和利用提供了一定的理论基础。

本文引用格式

赵倪慧 , 蒋琳 , 张丁 , 段江波 , 丁祥 , 侯怡铃 . 草黄口蘑多糖对S180荷瘤小鼠抗肿瘤活性分子机制研究[J]. 食品与发酵工业, 2024 , 50(11) : 27 -37 . DOI: 10.13995/j.cnki.11-1802/ts.035686

Abstract

As one of the main functional components of Tricholoma, polysaccharides have activities such as immune regulation, antioxidant and anti-tumor effects.To clarify the structure and the molecular mechanisms of anti-tumor activity of polysaccharide from Tricholoma lascivum (Fr.) Gillet on S180 tumor-bearing mice, the Tricholoma lascivum (Fr.) Gillet polysaccharide (TLG-1) extracted from the fruiting body of Tricholoma lascivum (Fr.) Gillet by hot water extraction method was used as the experimental material, the structure of TLG-1 was preliminarily analyzed, S180 tumor bearing-mice were used as models to detect anti-tumor activity in vivo, the total RNA of S180 tumor tissue was also sequenced using RNA sequencing.Results showed that TLG-1 had the weight-average molecular weight of 13 442 Da and was composed of xylose, mannose, glucose, and galactose in a ratio of 1.57∶1.45∶2.84∶4.14.TLG-1 could significantly inhibit the growth of S180 tumors in mice (P<0.01), with a tumor inhibition rate of 53.8%.Transcriptome sequencing analysis showed that TLG-1 could significantly up-regulate genes such as mt-Co1, Prlr, Foxa1, and down-regulate genes such as Pitx2, Rplp1, Eef1a1, and Lgals1, affecting the metabolic pathways of S180 tumor cells, regulating the cell cycle, and inhibiting epithelial-mesenchymal transition process.Gene ontology enrichment analysis showed that TLG-1 could activate cytokine-mediated signaling pathways and trigger cellular immunity.Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that genes such as Il21, Il12rb2, Il12b, Il2ra, Il2rb, Il2rg, Il15ra, and Ifng in the Jak-STAT signaling pathway were significantly up-regulated.TLG-1 could enhance the anti-tumor immune response of mice by transforming tumor-associated macrophage phenotype, and secreting interferon-γ.The results could provide a theoretical basis for the development and utilization of TLG-1.

参考文献

[1] 江飞凤, 谭晓辉, 胡鹏刚, 等.超声-微波协同提取柚子皮多糖工艺优化及单糖组成、结构和抗氧化活性分析[J].食品与发酵工业, 2021, 47(2):196-204.
JIANG F F, TAN X H, HU P G, et al.Optimization of ultrasonic-microwave extraction process of pomelo peel polysaccharide and analysis of monosaccharide composition, structure and antioxidant activity[J].Food and Fermentation Industries, 2021, 47(2):196-204.
[2] KUMAR A, JAITAK V.Natural products as multidrug resistance modulators in cancer[J].European Journal of Medicinal Chemistry, 2019, 176:268-291.
[3] 李勤, 张嫚, 孟祥珍.香菇多糖注射液结合吉非替尼对非小细胞肺癌疗效、肺功能、不良反应影响研究[J].中华中医药学刊, 2021, 39(4):163-166.
LI Q, ZHANG M, MENG X Z.Effects of lentinan injection combined with gefitinib on efficacy, lung function and side effects of non-small cell lung cancer patients[J].Chinese Archives of Traditional Chinese Medicine, 2021, 39(4):163-166.
[4] FOLEY G E, DROLET B P.Sustained propagation of sarcoma 180 in tissue culture[J].Proceedings of the Society for Experimental Biology and Medicine, 1956, 92(2):347-352.
[5] CHIHARA G, MAEDA Y, HAMURO J, et al.Inhibition of mouse sarcoma 180 by polysaccharides from Lentinus edodes (Berk.) Sing[J].Nature, 1969, 222(5194):687-688.
[6] 姜爽, 徐婧瑶, 苏鑫, 等.山慈菇多糖的免疫调节作用及对小鼠骨肉瘤细胞S180体内生长抑制作用[J].食品科学, 2018, 39(13):216-221.
JIANG S, XU J Y, SU X, et al.Effects of pseudobulbus cremastrae seu pleiones polysaccharide on the regulation of immune function and the inhibition of tumor growth in sarcoma S180 tumor-bearing mice[J].Food Science, 2018, 39(13):216-221.
[7] 季宇彬, 汲晨锋.芦笋多糖对肿瘤小鼠红细胞离子通道活性的影响[J].中国食品学报, 2014, 14(7):27-31.
JI Y B, JI C F.Effect of Asparagus polysaccharide on erythrocyte ion channel in tumor model mice[J].Journal of Chinese Institute of Food Science and Technology, 2014, 14(7):27-31.
[8] 刘燕琳, 刘海燕, 常金, 等.桑黄多糖对肉瘤S180细胞体内外的抑瘤作用[J].中国药房, 2017, 28(22):3069-3072.
LIU Y L, LIU H Y, CHANG J, et al.Antitumor effect of Phellinus Linteus polysaccharide on sarcoma S180 cells in vivo and in vitro[J].China Pharmacy, 2017, 28(22):3069-3072.
[9] 陈茜, 侯怡铃, 杨彤, 等.灰褐纹口蘑多糖对免疫细胞的调节作用[J].食用菌学报, 2021, 28(4):64-74.
CHEN X, HOU Y L, YANG T, et al.Regulative effects of Tricholoma sinoportentosum polysaccharide extract on immune cells[J].Acta Edulis Fungi, 2021, 28(4):64-74.
[10] YOU L J, GAO Q, FENG M Y, et al.Structural characterisation of polysaccharides from Tricholoma matsutake and their antioxidant and antitumour activities[J].Food Chemistry, 2013, 138(4):2242-2249.
[11] 郭华, 刁全平, 张博, 等.杨树口蘑多糖的超声波辅助提取工艺及其抗氧化活性[J].食品工业科技, 2018, 39(5):180-184.
GUO H, DIAO Q P, ZHANG B, et al.Optimization of ultrasonic-assisted extraction and antioxidant activity of polysaccharides from Tricholoma populinum[J].Science and Technology of Food Industry, 2018, 39(5):180-184.
[12] YANG H R, CHEN L H, ZENG Y J.Structure, antioxidant activity and in vitro hypoglycemic activity of a polysaccharide purified from Tricholoma matsutake[J].Foods, 2021, 10(9):2184.
[13] MEHMOOD S, ZHOU L Y, WANG X F, et al.Structural elucidation and antioxidant activity of a novel heteroglycan from Tricholoma lobayense[J].Journal of Carbohydrate Chemistry, 2019, 38(3):192-211.
[14] 张玉, 张琪琳, 王静林, 等.香菇多糖构效关系、抗肿瘤作用机制及药代动力学研究进展[J].中国医院药学杂志, 2023, 43(7):804-812.
ZHANG Y, ZHANG Q L, WANG J L, et al.Advances in structure-activity relationship, anti-tumor mechanism and pharmacokinetics of lentinan[J].Chinese Journal of Hospital Pharmacy, 2023, 43(7):804-812.
[15] HOU Y L, DING X, HOU W R, et al.Structure elucidation and antitumor activity of a new polysaccharide from Maerkang Tricholoma matsutake[J].International Journal of Biological Sciences, 2017, 13(7):935-948.
[16] ZHANG N, YANG B, MAO K M, et al.Comparison of structural characteristics and bioactivity of Tricholoma mongolicum Imai polysaccharides from five extraction methods[J].Frontiers in Nutrition, 2022, 9:962584.
[17] 杜秀菊, 张劲松, 潘迎捷.核磁共振技术在食用菌多糖结构分析中的作用[J].中国食用菌, 2010, 29(1):3-6;19.
DU X J, ZHANG J S, PAN Y J.Application of the NMR techniques in structural analysis of polysaccharide from edible fungi[J].Edible Fungi of China, 2010, 29(1):3-6;19.
[18] ALHUSSONA A J, ALMANDEL A S, ALI M M, et al.Genetic variations of the mtCOX1 gene for Iraqi patients with tetralogy of fallot[J].Current Pediatric Research, 2021, 25(10):981-986.
[19] ORONSKY B T, ORONSKY N, FANGER G R, et al.Follow the ATP:Tumor energy production:A perspective[J].Anti-Cancer Agents in Medicinal Chemistry, 2014, 14(9):1187-1198.
[20] XIE C J, CAO K, PENG D X, et al.RPLP1 is highly expressed in hepatocellular carcinoma tissues and promotes proliferation, invasion and migration of human hepatocellular carcinoma Hep3b cells[J].Experimental and Therapeutic Medicine, 2021, 22(1):752.
[21] LI J M, TSENG C W, LIN C C, et al.Upregulation of LGALS1 is associated with oral cancer metastasis[J].Therapeutic Advances in Medical Oncology, 2018, 10:1758835918794622.
[22] HUANG J, ZHENG C Q, SHAO J, et al.Overexpression of eEF1A1 regulates G1-phase progression to promote HCC proliferation through the STAT1-cyclin D1 pathway[J].Biochemical and Biophysical Research Communications, 2017, 494(3-4):542-549.
[23] 黄佩琦. 催乳素受体PRLR在胰腺导管腺癌中的作用及分子机制研究[D].上海:上海交通大学, 2020.
HUANG P Q.The role and underlying molecular mechanism of prolactin receptor PRLR in pancreatic ductal adenocarcinoma[D].Shanghai:Shanghai Jiao Tong University, 2020.
[24] LIU Y, HUANG Y, ZHU G Z.Cyclin A1 is a transcriptional target of PITX2 and overexpressed in papillary thyroid carcinoma[J].Molecular and Cellular Biochemistry, 2013, 384(1-2):221-227.
[25] LIN M X, PAN J, CHEN Q, et al.Overexpression of FOXA1 inhibits cell proliferation and EMT of human gastric cancer AGS cells[J].Gene, 2018, 642:145-151.
[26] BOLLI R, DAWN B, XUAN Y T.Role of the JAK-STAT pathway in protection against myocardial ischemia/reperfusion injury[J].Trends in Cardiovascular Medicine, 2003, 13(2):72-79.
[27] YANG Y, LUNDQVIST A.Immunomodulatory effects of IL-2 and IL-15;Implications for cancer immunotherapy[J].Cancers, 2020, 12(12):3586.
[28] LEONARD W J, WAN C K.IL-21 signaling in immunity[J].F1000Research, 2016, 5:F1000 Faculty Rev-F1000 Faculty 224.
[29] NGUYEN K G, VRABEL M R, MANTOOTH S M, et al.Localized interleukin-12 for cancer immunotherapy[J].Frontiers in Immunology, 2020, 11:575597.
[30] 刘玲, 焦鹏涛, 王萌, 等.鸡干扰素γ与白介素2对外周血中Th1细胞分化相关细胞因子的影响[J].生物工程学报, 2022, 38(9):3329-3343.
LIU L, JIAO P T, WANG M, et al.Effects of chicken interferon-γ and interleukin-2 on cytokines related to Th1 cell differentiation in peripheral blood[J].Chinese Journal of Biotechnology, 2022, 38(9):3329-3343.
[31] SU S Y, DING X, HOU Y L, et al.Structure elucidation, immunomodulatory activity, antitumor activity and its molecular mechanism of a novel polysaccharide from Boletus reticulatus Schaeff[J].Food Science and Human Wellness, 2023, 12(2):647-661.
[32] DONG M M, HOU Y L, DING X.Structure identification, antitumor activity and mechanisms of a novel polysaccharide from Ramaria flaccida (Fr.) Quél[J].Oncology Letters, 2020, 20(3):2169-2182.
[33] 鲁艳, 黄瑶, 叶姿妤, 等.转录组分析探讨揭示羊肚菌多糖ME-X抗S180肿瘤的分子机制[J].四川农业大学学报, 2022, 40(4):519-528.
LU Y, HUANG Y, YE Z Y, et al.Transcriptomes analysis revealed the molecular mechanism about the anti-S180 tumor activity of the polysaccharide ME-X from Morchella esculenta[J].Journal of Sichuan Agricultural University, 2022, 40(4):519-528.
[34] ZHANG S S, NIE S P, HUANG D F, et al.Polysaccharide from Ganoderma atrum evokes antitumor activity via Toll-like receptor 4-mediated NF-κB and mitogen-activated protein kinase signaling pathways[J].Journal of Agricultural and Food Chemistry, 2013, 61(15):3676-3682.
[35] MORRIS R, KERSHAW N J, BABON J J.The molecular details of cytokine signaling via the JAK/STAT pathway[J].Protein Science: a Publication of the Protein Society, 2018, 27(12):1984-2009.
文章导航

/