植物化学物在肿瘤微环境中的作用研究进展

doi:10.11904/j.issn.1002-3070.2025.03.010

摘要/Abstract

摘要： 植物化学物是来源于自然界的天然产物,有研究发现其可以通过多种途径抑制不同肿瘤的发生发展。研究揭示,肿瘤微环境作为驱动肿瘤恶性进展的关键调控靶标,其与植物化学物的协同抗肿瘤效应已成为研究焦点。因此,本文将近年来植物化学物在肿瘤微环境中的作用及其可能机制的研究现状和进展进行综述。

关键词: 植物化学物, 肿瘤, 肿瘤微环境

Abstract: Phytochemicals are natural products derived from nature.Numerous studies have demonstrated that they can inhibit the occurrence and development of different tumors through various pathways.Recent studies have revealed that the tumor microenvironment is a key regulatory target that drives the malignant progression of tumors,and its synergistic anti-tumor effects with phytochemicals has become a research focus.Therefore,this article reviews the current status and progress of research on the role of phytochemicals in the tumor microenvironment and its possible mechanisms in recent years.

Key words: Phytochemicals, Tumor, Tumor microenvironment

中图分类号:

叶倩妮, 李娟, 王发琳, 刘家仁. 植物化学物在肿瘤微环境中的作用研究进展[J]. 实用肿瘤学杂志, 2025, 39(3): 245-250.

YE Qianni, LI Juan, WANG Falin, LIU Jiaren. Research progress on the role of phytochemicals in tumor microenvironment[J]. Journal of Practical Oncology, 2025, 39(3): 245-250.

参考文献

1 Bishayee A,Thoppil RJ,Waghray A,et al.Dietary phytochemicals in the chemoprevention and treatment of hepatocellular carcinoma:in vivo evidence,molecular targets,and clinical relevance[J].Curr Cancer Drug Targets,2012,12(9):1191-1232.
2 Lee J,Han Y,Wang W,et al.Phytochemicals in cancer immune checkpoint inhibitor therapy[J].Biomolecules,2021,11(8):1107-1141.
3 Wang F,Chang X,Shi Y,et al.β-Ionone enhances the inhibitory effects of 5-fluorouracil on the proliferation of gastric adenocarcinoma cells by the GSK-3β signaling pathway[J].PLoS One,2024,19(9):e0309014.
4 Zubair H,Khan MA,Anand S,et al.Modulation of the tumor microenvironment by natural agents:implications for cancer prevention and therapy[J].Semin Cancer Biol,2022,80:237-255.
5 常晓霞,宋冰冰,刘家仁.植物化学物增加肿瘤细胞对化疗药物敏感性的研究进展[J].实用肿瘤学杂志,2019,33(1):67-72.
6 Zhu H,Wang FL,Zhang S,et al.γ-Tocotrienol enhances autophagy of gastric cancer cells by the regulation of GSK3β/β-Catenin pathway[J].Mol Carcinog,2024:1-13.
7 Dong HW,Wang K,Chang XX,et al.Beta-ionone-inhibited proliferation of breast cancer cells by inhibited COX-2 activity[J].Arch Toxicol,2019,93(10):2993-3003.
8 Dong HW,Zhang S,Sun WG,et al.β-Ionone arrests cell cycle of gastric carcinoma cancer cells by a MAPK pathway[J].Arch Toxicol,2013,87(10):1797-1808.
9 Tredan O,Galmarini CM,Patel K,et al.Drug resistance and the solid tumor microenvironment[J].J Natl Cancer Inst,2007,99(19):1441-1454.
10 Xiao Y,Yu D.Tumor microenvironment as a therapeutic target in cancer[J].Pharmacol Ther,2021,221:107753.
11 Wu T,Dai Y.Tumor microenvironment and therapeutic response[J].Cancer Lett,2017,387:61-68.
12 Anderson NM,Simon MC.The tumor microenvironment[J].Curr Biol,2020,30(16):R921-R925.
13 Hanahan D,Coussens Lisa M.Accessories to the crime:functions of cells recruited to the tumor microenvironment[J].Cancer Cell,2012,21(3):309-322.
14 de Visser KE,Joyce JA.The evolving tumor microenvironment:From cancer initiation to metastatic outgrowth[J].Cancer Cell,2023,41(3):374-403.
15 Komohara Y,Jinushi M,Takeya M.Clinical significance of macrophage heterogeneity in human malignant tumors[J].Cancer Sci,2013,105(1):1-8.
16 Huang YJ,Yang CK,Wei PL,et al.Ovatodiolide suppresses colon tumorigenesis and prevents polarization of M2 tumor-associated macrophages through YAP oncogenic pathways[J].J Hematol Oncol,2017,10(1):60-77.
17 Cheng Y,Zhong X,Nie X,et al.Glycyrrhetinic acid suppresses breast cancer metastasis by inhibiting M2-like macrophage polarization via activating JNK1/2 signaling[J].Phytomedicine,2023,114:577-587.
18 Farhood B,Najafi M,Mortezaee K.CD8+ cytotoxic T lymphocytes in cancer immunotherapy:A review[J].J Cell Physiol,2018,234(6):8509-8521.
19 Ryan NM,Lamenza FF,Upadhaya P,et al.Black raspberry extract inhibits regulatory T-cell activity in a murine model of head and neck squamous cell carcinoma chemoprevention[J].Front Immunol,2022,13:932742.
20 Shu G,Jiang S,Mu J,et al.Antitumor immunostimulatory activity of polysaccharides from Panax japonicus C.A.Mey:Roles of their effects on CD4+T cells and tumor associated macrophages[J].Int J Biol Macromol,2018,111:430-439.
21 Long T,Liu Z,Shang J,et al.Polygonatum sibiricum polysaccharides play anti-cancer effect through TLR4-MAPK/NF-κB signaling pathways[J].Int J Biol Macromol,2018,111:813-821.
22 Liu L,Lim MA,Jung S-N,et al.The effect of Curcumin on multi-level immune checkpoint blockade and T cell dysfunction in head and neck cancer[J].Phytomedicine,2021,92:153758.
23 Lyu C,Wang L,Stadlbauer B,et al.Identification of EZH2 as cancer stem cell marker in clear cell renal cell carcinoma and the anti-tumor effect of epigallocatechin-3-gallate(EGCG)[J].Cancers,2022,14(17):4200-4227.
24 Salminen A,Kaarniranta K,Kauppinen A.Phytochemicals inhibit the immunosuppressive functions of myeloid-derived suppressor cells(MDSC):impact on cancer and age-related chronic inflammatory disorders[J].Int Immunopharmacol,2018,61:231-240.
25 Gabrilovich DI,Ostrand-Rosenberg S,Bronte V.Coordinated regulation of myeloid cells by tumours[J].Nat Rev Immunol,2012,12(4):253-268.
26 Yin SY,Jian FY,Chen YH,et al.Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis[J].Nat Commun,2016,7(1):11311.
27 Zhang F,Dong W,Zeng W,et al.Naringenin prevents TGF-β1 secretion from breast cancer and suppresses pulmonary metastasis by inhibiting PKC activation[J].Breast Cancer Res,2016,18(1):38.
28 Zeng AQ,Yu Y,Yao YQ,et al.Betulinic acid impairs metastasis and reduces immunosuppressive cells in breast cancer models[J].Oncotarget,2018,9(3):3794-3804.
29 Kennel KB,Bozlar M,De Valk AF,et al.Cancer-associated fibroblasts in inflammation and antitumor immunity[J].Clin Cancer Res,2023,29(6):1009-1016.
30 Costa A,Kieffer Y,Scholer-Dahirel A,et al.Fibroblast heterogeneity and immunosuppressive environment in human breast cancer[J].Cancer Cell,2018,33(3):463-479.e410.
31 Ham IH,Lee D,Hur H.Role of cancer-associated fibroblast in gastric cancer progression and resistance to treatments[J].J Oncol,2019,2019:1-11.
32 Hu X,Peng X,Zhang Y,et al.Shikonin reverses cancer-associated fibroblast-induced gemcitabine resistance in pancreatic cancer cells by suppressing monocarboxylate transporter 4-mediated reverse Warburg effect[J].Phytomedicine,2024,123:155214.
33 Liu Q,Guo Z,Li G,et al.Cancer stem cells and their niche in cancer progression and therapy[J].Cancer Cell Int,2023,23(1):305.
34 Chan MM,Chen R,Fong D.Targeting cancer stem cells with dietary phytochemical-repositioned drug combinations[J].Cancer Lett,2018,433:53-64.
35 Jo MK,Moon CM,Kim EJ,et al.Suppressive effect of α-mangostin for cancer stem cells in colorectal cancer via the Notch pathway[J].BMC Cancer,2022,22(1):341.
36 Xie C,Liang C,Wang R,et al.Resveratrol suppresses lung cancer by targeting cancer stem-like cells and regulating tumor microenvironment[J].J Nutr Biochem,2023,112:109211.
37 Propper DJ,Balkwill FR.Harnessing cytokines and chemokines for cancer therapy[J].Nat Rev Clin Oncol,2022,19(4):237-253.
38 Oppenheim JJ.Cytokines:past,present,and future[J].Int J Hematol,2001,74(1):3-8.
39 Xia T,Li J,Ren X,et al.Research progress of phenolic compounds regulating IL‐6 to exert antitumor effects[J].Phytother Res,2021,35(12):6720-6734.
40 Verdura S,Cuyàs E,Llorach-Parés L,et al.Silibinin is a direct inhibitor of STAT3[J].Food Chem Toxicol,2018,116:161-172.
41 Subramaniam S,Anandha Rao JS,Ramdas P,et al.Reduced infiltration of regulatory T cells in tumours from mice fed daily with gamma-tocotrienol supplementation[J].Clin Exp Immunol,2021,206(2):161-172.
42 Liu QM,Xu SS,Li L,et al.In vitro and in vivo immunomodulatory activity of sulfated polysaccharide from Porphyra haitanensis[J].Carbohydrate Polymers,2017,165:189-196.
43 Ahmad A,Nawaz MI.Molecular mechanism of VEGF and its role in pathological angiogenesis[J].J Cell Biochem,2022,123(12):1938-1965.
44 Gu Y,Becker V,Qiu M,et al.Brassinin promotes the degradation of Tie2 and FGFR1 in endothelial cells and inhibits triple-negative breast cancer angiogenesis[J].Cancers,2022,14(14):3540.
45 Yuan M,Meng W,Liao W,et al.Andrographolide antagonizes TNF-α-induced IL-8 via inhibition of NADPH Oxidase/ROS/NF-κB and Src/MAPKs/AP-1 Axis in human colorectal cancer HCT116 cells[J].J Agric Food Chem,2018,66(20):5139-5148.
46 Zhang L,Cheng X,Gao Y,et al.Curcumin inhibits metastasis in human papillary thyroid carcinoma BCPAP cells via down-regulation of the TGF-β/Smad2/3 signaling pathway[J].Exp Cell Res,2016,341(2):157-165.
47 Wang Q,Xu H,Zhao X.Baicalin inhibits human cervical cancer cells by suppressing protein kinase C/signal transducer and activator of transcription(PKC/STAT3)signaling pathway[J].Med Sci Monit,2018,24:1955-1961.
48 Wu HT,Lin J,Liu YE,et al.Luteolin suppresses androgen receptor-positive triple-negative breast cancer cell proliferation and metastasis by epigenetic regulation of MMP9 expression via the Akt/mTOR signaling pathway[J].Phytomedicine,2021,81:153437.
49 Al Alawi R,Alhamdani MSS,Hoheisel JD,et al.Antifibrotic and tumor microenvironment modulating effect of date palm fruit(Phoenix dactylifera L.)extracts in pancreatic cancer[J].Biomed Pharmacother,2020,121:109522.
50 Al-Abdallat K,Obeidat M,Ababneh NA,et al.Phytochemical analysis and anticancer properties of drimia maritima bulb extracts on colorectal cancer cells[J].Molecules,2023,28(3):1215-1233.

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