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天津中医药大学,天津 301617
Received:28 October 2021,
Published Online:14 December 2021,
Published:20 February 2022
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王栋,王方园,时浩洋等.巨噬细胞极化与中药抗肿瘤机制研究进展[J].中国实验方剂学杂志,2022,28(04):246-253.
WANG Dong,WANG Fang-yuan,SHI Hao-yang,et al.Macrophage Polarization and Anti-tumor Mechanism of Chinese Medicine:A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(04):246-253.
王栋,王方园,时浩洋等.巨噬细胞极化与中药抗肿瘤机制研究进展[J].中国实验方剂学杂志,2022,28(04):246-253. DOI: 10.13422/j.cnki.syfjx.20220428.
WANG Dong,WANG Fang-yuan,SHI Hao-yang,et al.Macrophage Polarization and Anti-tumor Mechanism of Chinese Medicine:A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(04):246-253. DOI: 10.13422/j.cnki.syfjx.20220428.
巨噬细胞是一类具有较强可塑性的天然免疫细胞,巨噬细胞极化主要是通过改变其表型和相关功能,对微环境中刺激作出相应的免疫反应。近年来研究发现巨噬细胞极化通过核转录因子-
κ
B(NF-
κ
B),c-Jun氨基末端激酶(JNK),蛋白激酶B(Akt),丝裂原活化蛋白激酶(MAPK),信号传导及转录激活蛋白6(STAT6),Wnt/
β
-连环蛋白(
β
-catenin),哺乳动物雷帕霉素靶蛋白(mTOR)等多种信号通路及调节因子粒细胞-巨噬细胞集落刺激因子(GM-CSF),白细胞介素(IL)-4,IL-10,转化生长因子-
β
(TGF-
β
),肿瘤坏死因子-
α
(TNF-
α
),
γ
干扰素(IFN-
γ
)等参与了骨关节炎、糖尿病、冠心病、乳腺癌、结直肠癌、肺癌等多种疾病的发生发展过程,尤其是恶性肿瘤转移及治疗药物耐药等,而中医药在恶性肿瘤的防治中也占有一席之地。因此,近年来中药及有效成分抗肿瘤具体作用机制的研究成为研究热点。肿瘤微环境对肿瘤的发生发展至关重要,肿瘤相关巨噬细胞的极化参与肿瘤细胞的增殖、凋亡、转移等过程。因此,靶向调控肿瘤相关巨噬细胞的极化可能是恶性肿瘤的临床治疗的新靶点。结合近3年国内外相关文献,该文从巨噬细胞极化,巨噬细胞极化的相关通路及调节因子,巨噬细胞极化与乳腺癌、结直肠癌、肺癌等,巨噬细胞极化与中药、中药有效成分及自拟方/经方等抗肿瘤作用4个方面对巨噬细胞极化与中药抗肿瘤机制进行综述,以期为中医药抗肿瘤的临床治疗、基础研究及中药新药的研发提供一定的思路。
Macrophages are natural immune cells with strong plasticity. The polarization of macrophages mainly responds to stimuli in the microenvironment by changing their phenotype and related functions. In recent years, studies have found that the polarization of macrophages is involved in the occurrence and development of various diseases such as bone arthritis, skin diseases, diabetes, coronary heart disease, breast cancer, colorectal cancer, and lung cancer, especially the metastasis of malignancies and drug resistance, through multiple signaling pathways, including nuclear factor kappa-B(NF-
κ
B), c-Jun
N
-terminal kinase(JNK), protein kinase B (Akt), mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 6 (STAT6), Wnt/
β
-catenin, and mammalian target of rapamycin (mTOR) and regulatory factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4, IL-10, transforming growth factor
(TGF)-
β
, tumor necrosis factor(TNF)-
α
, and interferon-
γ(
IFN-
γ
). Chinese medicine is also pivotal in the prevention and treatment of malignancies. In recent years, therefore, the specific anti-tumor mechanism of Chinese medicine and its active ingredients has become a research hotspot. The tumor microenvironment is crucial to the occurrence and development of tumors. The polarization of tumor-associated macrophages is involved in the proliferation, apoptosis, and metastasis of tumor cells. Therefore, targeted regulation of the polarization of tumor-associated macrophages is a potential target for clinical treatment of malignancies. Based on the research articles published in the past three years, this article reviewed macrophage polarization and the anti-tumor mechanism of Chinese medicine from four perspectives, i.e., macrophage polarization, related pathways and regulatory factors of macrophage polarization, macrophage polarization and breast cancer, colorectal cancer, and lung cancer, and macrophage polarization and anti-tumor effects of Chinese medicine, active ingredients of Chinese medicine, and self-formulated prescriptions/classic prescriptions. This study is expected to provide certain ideas for the clinical treatment, basic research, and development of new Chinese medicine in the treatment of tumors.
LOCATI M , CURTALE G , MANTOVANI A. Diversity , mechanisms , and significance of macrophage plasticity [J]. Annu Rev Pathol , 2020 , 15 ( 2 ): 123 - 147 .
YUNNA C , MENGRU H , LEI W , et al . Macrophage M1/M2 polarization [J]. Eur J Pharmacol , 2020 , 877 ( 35 ): 173090 - 173103 .
MOREIRA T C , MOSSER D M , GONÇALVES R . Macrophage polarization in intestinal inflammation and gut homeostasis [J]. Inflamm Res , 2020 , 69 ( 12 ): 1163 - 1172 .
ZHANG H , CAI D , BAI X . Macrophages regulate the progression of osteoarthritis [J]. Osteoarthritis Cartilage , 2020 , 28 ( 5 ): 555 - 561 .
LOUISELLE A E , NIEMIEC S M , ZGHEIB C , et al . Macrophage polarization and diabetic wound healing [J]. Transl Res , 2021 , 236 ( 10 ): 109 - 116 .
BARRETT T J . Macrophages in atherosclerosis regression [J]. Arterioscler Thromb Vasc Biol , 2020 , 40 ( 1 ): 20 - 33 .
LU C S , SHIAU A L , SU B H , et al . Oct4 promotes M2 macrophage polarization through upregulation of macrophage colony-stimulating factor in lung cancer [J]. J Hematol Oncol , 2020 , 13 ( 1 ): 62 - 70 .
SHU Y , QIN M , SONG Y , et al . M2 polarization of tumor-associated macrophages is dependent on integrin β 3 via peroxisome proliferator-activated receptor- γ up-regulation in breast cancer [J]. Immunology , 2020 , 160 ( 4 ): 345 - 356 .
LIU F , WANG C , HUANG H , et al . SEMA3A-mediated crosstalk between prostate cancer cells and tumor-associated macrophages promotes androgen deprivation therapy resistance [J]. Cell Mol Immunol , 2021 , 18 ( 3 ): 752 - 754
LE F , YANG L , HAN Y , et al . TPL inhibits the invasion and migration of drug-resistant ovarian cancer by targeting the PI3K/Akt/NF- κ B-signaling pathway to inhibit the polarization of M2 TAMs [J]. Front Oncol , 2021 , 3389 ( 11 ): 704001 - 704018 .
CHENG H , SUN L , SHEN D , et al . β -1,6 glucan converts tumor-associated macrophages into an M1-like phenotype [J]. Carbohydr Polym , 2020 , 247 ( 56 ): 116715 - 116783 .
MODEST D P , PANT S , SARTORE-BIANCHI A . Treatment sequencing in metastatic colorectal cancer [J]. Eur J Cancer , 2019 , 109 ( 1 ): 70 - 83 .
YAN J , HORNG T . Lipid metabolism in regulation of macrophage functions [J]. Trends Cell Biol , 2020 , 30 ( 12 ): 979 - 989 .
DÍAZ-BULNES P , SAIZ M L , LÓPEZ-LARREA C , et al . Crosstalk between hypoxia and ER stress response: a key regulator of macrophage polarization [J]. Front Immunol , 2020 , 86 ( 10 ): 2951 - 2963 .
BOUTILIER A J , ELSAWA S F . Macrophage polarization states in the tumor microenvironment [J]. Int J Mol Sci , 2021 , 22 ( 13 ): 6995 - 7002 .
PFLUG K M , SITCHERAN R . Targeting NF- κ B-inducing kinase (NIK) in immunity, inflammation, and cancer [J]. Int J Mol Sci , 2020 , 21 ( 22 ): 8470 - 8483 .
HU Y , GUI Z , ZHOU Y , et al . Quercetin alleviates rat osteoarthritis by inhibiting inflammation and apoptosis of chondrocytes, modulating synovial macrophages polarization to M2 macrophages [J]. Free Radic Biol Med , 2019 , 145 ( 2 ): 146 - 160 .
LIU S , SHEN H , LI J , et al . Loganin inhibits macrophage M1 polarization and modulates sirt1/NF- κ B signaling pathway to attenuate ulcerative colitis [J]. Bioengineered , 2020 , 11 ( 1 ): 628 - 639 .
XU Z , HAN X , OU D , et al . Targeting PI3K/Akt/mTOR-mediated autophagy for tumor therapy [J]. Appl Microbiol Biotechnol , 2020 , 104 ( 2 ): 575 - 587 .
ZHAO S , MI Y , GUAN B , et al . Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer [J]. J Hematol Oncol , 2020 , 13 ( 1 ): 156 - 164 .
WEI Y , LIANG M , XIONG L , et al . PD-L1 induces macrophage polarization toward the M2 phenotype via ERK/Akt/mTOR [J]. Exp Cell Res , 2021 , 402 ( 2 ): 112575 - 112587 .
FURUE M . Regulation of skin barrier function via competition between AHR axis versus IL-13/IL-4-JAK-STAT6/STAT3 axis: pathogenic and therapeutic implications in atopic dermatitis [J]. J Clin Med , 2020 , 9 ( 11 ): 3741 - 3752 .
YANG T , WANG R , LIU H , et al . Berberine regulates macrophage polarization through IL-4-STAT6 signaling pathway in Helicobacter pylori-induced chronic atrophic gastritis [J]. Life Sci , 2021 , 266 ( 56 ): 118903 - 118916 .
许大勇 , 李云朋 , 魏景梅 , 等 . 黄芩苷通过调控巨噬细胞M2极化对脊髓损伤大鼠炎症反应的抑制作用 [J]. 吉林大学学报:医学版 , 2021 , 47 ( 1 ): 158 - 167 .
LU M , WANG Y , ZHAN X . The MAPK pathway-based drug therapeutic targets in pituitary adenomas [J]. Front Endocrinol (Lausanne) , 2019 , 10 ( 3 ): 330 - 339 .
WANG L , GONG Z , ZHANG X , et al . Gut microbial bile acid metabolite skews macrophage polarization and contributes to high-fat diet-induced colonic inflammation [J]. Gut Microbes , 2020 , 12 ( 1 ): 1 - 20 .
LIU L , GUO H , SONG A , et al . Progranulin inhibits LPS-induced macrophage M1 polarization via NF- к B and MAPK pathways [J]. BMC Immunol , 2020 , 21 ( 1 ): 32 - 41 .
BIAN J , DANNAPPEL M , WAN C , et al . Transcriptional regulation of Wnt/ β -catenin pathway in colorectal cancer [J]. Cells , 2020 , 9 ( 9 ): 2125 - 2139 .
TIAN X , WU Y , YANG Y , et al . Long noncoding RNA LINC00662 promotes M2 macrophage polarization and hepatocellular carcinoma progression via activating Wnt/ β -catenin signaling [J]. Mol Oncol , 2020 , 14 ( 2 ): 462 - 483 .
巩奇明 , 姜艳 , 卢俊玲 , 等 . Fractalkine通过激活Wnt/ β -catenin信号通路抑制脂多糖诱导的巨噬细胞M1型极化 [J]. 南方医科大学学报 , 2020 , 40 ( 12 ): 1726 - 1731 .
FU L Q , DU W L , CAI M H , et al . The roles of tumor-associated macrophages in tumor angiogenesis and metastasis [J]. Cell Immunol , 2020 , 353 ( 49 ): 104119 - 104133 .
NASIM F , SABATH B F , EAPEN G A . Lung cancer [J]. Med Clin North Am , 2019 , 103 ( 3 ): 463 - 473 .
MATHIYALAGAN R , WANG C , KIM Y J , et al . Preparation of polyethylene glycol-ginsenoside Rh 1 and Rh 2 conjugates and their efficacy against lung cancer and inflammation [J]. Molecules , 2019 , 24 ( 23 ): 4367 - 4379 .
ALVÁN MORALES M A , BARRERA RODRÍGUEZ R , SANTIAGO CRUZ J R , et al . Overview of new treatments with immunotherapy for breast cancer and a proposal of a combination therapy [J]. Molecules , 2020 , 25 ( 23 ): 5686 - 5699 .
HUANG Y J , WANG K L , CHEN H Y , et al . Protective effects of epigallocatechin gallate (EGCG) on endometrial, breast, and ovarian cancers [J]. Biomolecules , 2020 , 10 ( 11 ): 1481 - 1494 .
TEO M Y , RATHKOPF D E , KANTOFF P . Treatment of advanced prostate cancer [J]. Annu Rev Med , 2019 , 70 ( 6 ): 479 - 499 .
LIU J , DING D , JIANG Z , et al . Long non-coding RNA CCAT1/miR-148a/PKC ζ prevents cell migration of prostate cancer by altering macrophage polarization [J]. Prostate , 2019 , 79 ( 1 ): 105 - 112 .
CHARKHCHI P , CYBULSKI C , GRONWALD J , et al . CA125 and ovarian cancer: a comprehensive review [J]. Cancers (Basel) , 2020 , 12 ( 12 ): 3730 - 3742 .
BAI Y , YIN K , SU T , et al . CTHRC1 in ovarian cancer promotes M2-like polarization of tumor-associated macrophages via regulation of the STAT6 signaling pathway [J]. Onco Targets Ther , 2020 , 147 ( 13 ): 5743 - 5753 .
DARIYA B , ALIYA S , MERCHANT N , et al . Colorectal cancer biology, diagnosis, and therapeutic approaches [J]. Crit Rev Oncog , 2020 , 25 ( 2 ): 71 - 94 .
LIU Q , YANG C , WANG S , et al . Wnt5a-induced M2 polarization of tumor-associated macrophages via IL-10 promotes colorectal cancer progression [J]. Cell Commun Signal , 2020 , 18 ( 1 ): 51 - 63 .
颜彬 , 周钱梅 . 肿瘤相关巨噬细胞参与化疗耐药及中医药干预研究进展 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 17 ): 193 - 202 .
李灿涛 , 卢颖裕 , 陈勇儿 , 等 . 巴戟天对人源结肠癌细胞HCT-116移植瘤的抑制作用及机制初步探讨 [J]. 食品工业科技 , 2021 , doi: 10.13386/j.issn1002-0306.2021050055 http://dx.doi.org/10.13386/j.issn1002-0306.2021050055 .
DAI X , ZHANG X , CHEN W , et al . Dihydroartemisinin: a potential natural anticancer drug [J]. Int J Biol Sci , 2021 , 17 ( 2 ): 603 - 622 .
CHEN R , LU X , LI Z , et al . Dihydroartemisinin prevents progression and metastasis of head and neck squamous cell carcinoma by inhibiting polarization of macrophages in tumor microenvironment [J]. Onco Targets Ther , 2020 , 182 ( 13 ): 3375 - 3387 .
DENG X X , JIAO Y N , HAO H F , et al . Taraxacum mongolicum extract inhibited malignant phenotype of triple-negative breast cancer cells in tumor-associated macrophages microenvironment through suppressing IL-10/STAT3/PD-L1 signaling pathways [J]. J Ethnopharmacol , 2021 , 274 ( 35 ): 113978 - 113992 .
张琦君 , 邓海滨 , 车勇 , 等 . 肺岩宁方对Lewis荷瘤小鼠肿瘤相关性巨噬细胞极化的调控作用研究 [J]. 中医药导报 , 2021 , 27 ( 4 ): 1 - 4,19 .
姜涛 , 钱钧 , 朱伟 , 等 . 加味黄芪建中汤通过IL-33介导肿瘤相关巨噬细胞极化的研究 [J]. 中华中医药杂志 , 2019 , 34 ( 9 ): 4294 - 4297 .
HE S , WANG S , LIU S , et al . Baicalein potentiated m1 macrophage polarization in cancer through targeting PI3K γ / NF- κ B signaling [J]. Front Pharmacol , 2021 , 3389 ( 12 ): 743837 - 743849 .
LI J , CAI H , SUN H , et al . Extracts of Cordyceps sinensis inhibit breast cancer growth through promoting M1 macrophage polarization via NF- κ B pathway activation [J]. J Ethnopharmacol , 2020 , 260 ( 38 ): 112969 - 112985 .
YANG R , XIE Y , LI Q , et al . Ruyiping extract reduces lung metastasis in triple negative breast cancer by regulating macrophage polarization [J]. Biomed Pharmacother , 2021 , 141 ( 58 ): 111883 - 111897 .
JIN Z , SHEN C , ZHANG H , et al . Chinese medicine Xiaoshui decoction inhibits malignant pleural effusion in mice and mediates tumor-associated macrophage polarization by activating autophagy [J]. J Ethnopharmacol , 2020 , 249 ( 60 ): 112412 - 112426 .
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