Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Qingrexiaoji Recipe Regulates the Differentiation of M2 TAM via miR-29 in GC

Author(s): Yiqiong Zhang, Luting Chen, Yuchang Fei, Peifeng Chen and Lei Pan*

Volume 27, Issue 18, 2024

Published on: 16 October, 2023

Page: [2764 - 2775] Pages: 12

DOI: 10.2174/0113862073263776231009115524

Price: $65

Abstract

Background: Gastric cancer, one of the most familiar adenocarcinomas of the gastrointestinal tract, ranks third in the world in cancer-related deaths. Traditional Chinese medicine can suppress the growth of tumors, and the underlying mechanism may be associated with the tumor microenvironment. Here, we investigated the anti-cancer effects of the Qingrexiaoji recipe on gastric cancer and the underlying molecular mechanism.

Methods: An in vivo nude mouse model was established, and the expression of CD206, CD80, and M2 phenotype-related proteins (Arg-1, Fizz1) was obtained by flow cytometry and western blotting. The expressions of the M2 phenotype-related cytokines were examined by ELISA.

Results: Qingrexiaoji recipe inhibited gastric tumor growth and downregulated the expression of CD206, IFN-γ, IL-13, IL-4, and TNF-α in vivo. Qingrexiaoji recipe deceased M2 phenotypic polarization by upregulating microRNA (miR)-29a-3p level. Luciferase activity assays showed that HDAC4 is a potential target of miR-29a-3p. In cells co-transfected with HDAC4 siRNA and miR-29a-3p inhibitor and treated with IL-4 and Qingrexiaoji recipe, the miR-29a-3p inhibitorinduced increase of M2 phenotypic polarization was reversed.

Conclusion: In summary, these results suggested that the Qingrexiaoji recipe regulated M2 macrophage polarization by regulating miR-29a-3p/HDAC4, providing a different and innovative treatment for gastric cancer.

[1]
Johnston, F.M.; Beckman, M. Updates on management of gastric cancer. Curr. Oncol. Rep., 2019, 21(8), 67.
[http://dx.doi.org/10.1007/s11912-019-0820-4] [PMID: 31236716]
[2]
Smyth, E.C.; Nilsson, M.; Grabsch, H.I.; van Grieken, N.C.T.; Lordick, F. Gastric cancer. Lancet, 2020, 396(10251), 635-648.
[http://dx.doi.org/10.1016/S0140-6736(20)31288-5] [PMID: 32861308]
[3]
Patel, T.H.; Cecchini, M. Targeted therapies in advanced gastric cancer. Curr. Treat. Options Oncol., 2020, 21(9), 70.
[http://dx.doi.org/10.1007/s11864-020-00774-4] [PMID: 32725377]
[4]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[5]
Murata, M. Inflammation and cancer. Environ. Health Prev. Med., 2018, 23(1), 50.
[http://dx.doi.org/10.1186/s12199-018-0740-1] [PMID: 30340457]
[6]
Li, Y.; Xia, R.; Zhang, B.; Li, C. Chronic atrophic gastritis: A review. J. Environ. Pathol. Toxicol. Oncol., 2018, 37(3), 241-259.
[http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2018026839] [PMID: 30317974]
[7]
Piazuelo, M.B.; Riechelmann, R.P.; Wilson, K.T.; Algood, H.M.S. Resolution of gastric cancer-promoting inflammation: A novel strategy for anti-cancer therapy. Curr. Top. Microbiol. Immunol., 2019, 421, 319-359.
[http://dx.doi.org/10.1007/978-3-030-15138-6_13] [PMID: 31123895]
[8]
Xiang, Y.; Guo, Z.; Zhu, P.; Chen, J.; Huang, Y. Traditional Chinese medicine as a cancer treatment: Modern perspectives of ancient but advanced science. Cancer Med., 2019, 8(5), 1958-1975.
[http://dx.doi.org/10.1002/cam4.2108] [PMID: 30945475]
[9]
Wang, Y.; Zhang, Q.; Chen, Y.; Liang, C.L.; Liu, H.; Qiu, F.; Dai, Z. Antitumor effects of immunity-enhancing traditional Chinese medicine. Biomed. Pharmacother., 2020, 121, 109570.
[http://dx.doi.org/10.1016/j.biopha.2019.109570] [PMID: 31710893]
[10]
Yu, J.; Song, S.; Jiao, J.; Liu, X.; Zhu, H.; Xiu, L.; Sun, D.; Li, Q.; Yue, X. ZiYinHuaTan recipe inhibits cell proliferation and promotes apoptosis in gastric cancer by suppressing PI3K/AKT pathway. BioMed Res. Int., 2020, 2020, 1-10.
[http://dx.doi.org/10.1155/2020/2018162] [PMID: 32382534]
[11]
Yuan, M.; Zou, X.; Liu, S.; Xu, X.; Wang, H.; Zhu, M.; Xie, X.; Wang, H.; Wu, J.; Sun, Q. Modified Jian-pi-yang-zheng decoction inhibits gastric cancer progression via the macrophage immune checkpoint PI3Kγ. Biomed. Pharmacother., 2020, 129, 110440.
[http://dx.doi.org/10.1016/j.biopha.2020.110440] [PMID: 32768942]
[12]
Liu, X.; Ji, Q.; Deng, W.; Chai, N.; Feng, Y.; Zhou, L.; Sui, H.; Li, C.; Sun, X.; Li, Q. JianPi JieDu recipe inhibits epithelial-to-mesenchymal transition in colorectal cancer through TGF- β/smad mediated snail/E-cadherin expression. BioMed Res. Int., 2017, 2017, 1-11.
[http://dx.doi.org/10.1155/2017/2613198] [PMID: 28299321]
[13]
Dai, Y.; Qiang, W.; Yu, X.; Cai, S.; Lin, K.; Xie, L.; Lan, X.; Wang, D. Guizhi fuling decoction inhibiting the pi3k and mapk pathways in breast cancer cells revealed by HTS2 technology and systems pharmacology. Comput. Struct. Biotechnol. J., 2020, 18, 1121-1136.
[http://dx.doi.org/10.1016/j.csbj.2020.05.004] [PMID: 32489526]
[14]
Gong, H.; Chen, W.; Mi, L.; Wang, D.; Zhao, Y.; Yu, C.; Zhao, A. Qici Sanling decoction suppresses bladder cancer growth by inhibiting the Wnt/Β-catenin pathway. Pharm. Biol., 2019, 57(1), 507-513.
[http://dx.doi.org/10.1080/13880209.2019.1626449] [PMID: 31401919]
[15]
Chen, P.F.; Pan, L.; Jin, Y.Q. [Effects of qingre xiaoji recipe on the migration, chemotaxis, and tube formation capability of human lung adenocarcinoma cell induced human umbilical vein endothelial cells]. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih, 2013, 33(4), 497-501.
[PMID: 23841271]
[16]
Peng, F.; Xie, X.; Peng, C. Chinese herbal medicine-based cancer therapy: Novel anticancer agents targeting MicroRNAs to regulate tumor growth and metastasis. Am. J. Chin. Med., 2019, 47(8), 1711-1735.
[http://dx.doi.org/10.1142/S0192415X19500873] [PMID: 31801358]
[17]
Qiu, W.; Wang, Z.; Chen, R.; Shi, H.; Ma, Y.; Zhou, H.; Li, M.; Li, W.; Chen, H.; Zhou, H. Xiaoai Jiedu Recipe suppresses hepatocellular carcinogenesis through the miR‐200b-3p/Notch1 axis. Cancer Manag. Res., 2020, 12, 11121-11131.
[http://dx.doi.org/10.2147/CMAR.S269991] [PMID: 33173345]
[18]
Xiao, J.; Liu, L.; Zhong, Z.; Xiao, C.; Zhang, J. Mangiferin regulates proliferation and apoptosis in glioma cells by induction of microRNA-15b and inhibition of MMP-9 expression. Oncol. Rep., 2015, 33(6), 2815-2820.
[http://dx.doi.org/10.3892/or.2015.3919] [PMID: 25901555]
[19]
Wang, C.; Wang, J.; Gao, M.; Gao, P.; Gao, D.; Zhang, H.; Mu, X.; Qiao, M. Radix Ranunculi ternati: Review of its chemical constituents, pharmacology, quality control and clinical applications. J. Pharm. Pharmacol., 2022, 74(7), 930-952.
[http://dx.doi.org/10.1093/jpp/rgac018] [PMID: 35596792]
[20]
Wu, X.; Xu, N.; Ye, Z.; Zhao, Q.; Liu, J.; Li, J.; Wu, M.; Zheng, Y.; Li, X.; Li, W.; Zhang, T.; Hu, X.; Zhang, Q. Polysaccharide from Scutellaria barbata D. Don attenuates inflammatory response and microbial dysbiosis in ulcerative colitis mice. Int. J. Biol. Macromol., 2022, 206, 1-9.
[http://dx.doi.org/10.1016/j.ijbiomac.2022.02.119] [PMID: 35218798]
[21]
Zhou, W.; Wang, G.; Zhao, X.; Xiong, F.; Zhou, S.; Peng, J.; Cheng, Y.; Xu, S.; Xu, X. A multiplex qPCR gene dosage assay for rapid genotyping and large-scale population screening for deletional α-thalassemia. J. Mol. Diagn., 2013, 15(5), 642-651.
[http://dx.doi.org/10.1016/j.jmoldx.2013.05.007] [PMID: 23810501]
[22]
Wu, J.Y.; Huang, T.W.; Hsieh, Y.T.; Wang, Y.F.; Yen, C.C.; Lee, G.L.; Yeh, C.C.; Peng, Y.J.; Kuo, Y.Y.; Wen, H.T.; Lin, H.C.; Hsiao, C.W.; Wu, K.K.; Kung, H.J.; Hsu, Y.J.; Kuo, C.C. Cancer-derived succinate promotes macrophage polarization and cancer metastasis via succinate receptor. Mol. Cell, 2020, 77(2), 213-227.e5.
[http://dx.doi.org/10.1016/j.molcel.2019.10.023] [PMID: 31735641]
[23]
Cheng, H.; Wang, Z.; Fu, L.; Xu, T. Macrophage polarization in the development and progression of ovarian cancers: An overview. Front. Oncol., 2019, 9, 421.
[http://dx.doi.org/10.3389/fonc.2019.00421] [PMID: 31192126]
[24]
Wang, X.; Luo, G.; Zhang, K.; Cao, J.; Huang, C.; Jiang, T.; Liu, B.; Su, L.; Qiu, Z. Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN/PI3Kγ to promote pancreatic cancer metastasis. Cancer Res., 2018, 78(16), 4586-4598.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-3841] [PMID: 29880482]
[25]
Teng, F.; Tian, W.Y.; Wang, Y.M.; Zhang, Y.F.; Guo, F.; Zhao, J.; Gao, C.; Xue, F.X. Cancer-associated fibroblasts promote the progression of endometrial cancer via the SDF-1/CXCR4 axis. J. Hematol. Oncol., 2016, 9(1), 8.
[http://dx.doi.org/10.1186/s13045-015-0231-4] [PMID: 26851944]
[26]
Yin, M.; Shen, J.; Yu, S.; Fei, J.; Zhu, X.; Zhao, J.; Zhai, L.; Sadhukhan, A.; Zhou, J. Tumor-associated macrophages (TAMs): A critical activator in ovarian cancer metastasis. OncoTargets Ther., 2019, 12, 8687-8699.
[http://dx.doi.org/10.2147/OTT.S216355] [PMID: 31695427]
[27]
Yu, M.; Qi, B.; Xiaoxiang, W.; Xu, J.; Liu, X. Baicalein increases cisplatin sensitivity of A549 lung adenocarcinoma cells via PI3K/Akt/NF-κB pathway. Biomed. Pharmacother., 2017, 90, 677-685.
[http://dx.doi.org/10.1016/j.biopha.2017.04.001] [PMID: 28415048]
[28]
Yan, W.; Ma, X.; Zhao, X.; Zhang, S. Baicalein induces apoptosis and autophagy of breast cancer cells via inhibiting PI3K/AKT pathway in vivo and vitro. Drug Des. Devel. Ther., 2018, 12, 3961-3972.
[http://dx.doi.org/10.2147/DDDT.S181939] [PMID: 30510404]
[29]
Cai, J.; Yi, M.; Tan, Y.; Li, X.; Li, G.; Zeng, Z.; Xiong, W.; Xiang, B. Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-II. J. Exp. Clin. Cancer Res., 2021, 40(1), 190.
[http://dx.doi.org/10.1186/s13046-021-01995-7] [PMID: 34108030]
[30]
Notarte, K.I.R.; Quimque, M.T.J.; Macaranas, I.T.; Khan, A.; Pastrana, A.M.; Villaflores, O.B.; Arturo, H.C.P.; Pilapil, D.Y.H., IV; Tan, S.M.M.; Wei, D.Q.; Wenzel-Storjohann, A.; Tasdemir, D.; Yen, C.H.; Ji, S.Y.; Kim, G.Y.; Choi, Y.H.; Macabeo, A.P.G. Attenuation of lipopolysaccharide-induced inflammatory responses through inhibition of the NF-κB pathway and the increased NRF2 level by a flavonol-enriched n -butanol fraction from uvaria alba. ACS Omega, 2023, 8(6), 5377-5392.
[http://dx.doi.org/10.1021/acsomega.2c06451] [PMID: 36816691]
[31]
Kim, S.J.; Chung, W.S.; Kim, S.S.; Ko, S.G.; Um, J.Y. Antiinflammatory effect of Oldenlandia diffusa and its constituent, hentriacontane, through suppression of caspase-1 activation in mouse peritoneal macrophages. Phytother. Res., 2011, 25(10), 1537-1546.
[http://dx.doi.org/10.1002/ptr.3443] [PMID: 21394806]
[32]
Liao, H.; Ye, J.; Gao, L.; Liu, Y. The main bioactive compounds of Scutellaria baicalensis Georgi. for alleviation of inflammatory cytokines: A comprehensive review. Biomed. Pharmacother., 2021, 133, 110917.
[http://dx.doi.org/10.1016/j.biopha.2020.110917] [PMID: 33217688]
[33]
Lei, X.; Li, N.; Bai, Z.; Di, J.; Zhang, H.; Dong, P.; Zhang, P. Chemical constituent from the peel of Trichosanthes kirilowii Maxim and their NF-κB inhibitory activity. Nat. Prod. Res., 2021, 35(23), 5132-5137.
[http://dx.doi.org/10.1080/14786419.2020.1786825] [PMID: 32744101]
[34]
Yu, M.; Chen, T.T.; Zhang, T.; Jia, H.M.; Li, J.J.; Zhang, H.W.; Zou, Z.M. Anti-inflammatory constituents in the root and rhizome of Polygonum cuspidatum by UPLC-PDA-QTOF/MS and lipopolysaccharide-activated RAW264.7 macrophages. J. Pharm. Biomed. Anal., 2021, 195, 113839.
[http://dx.doi.org/10.1016/j.jpba.2020.113839] [PMID: 33388645]
[35]
Shen, S.; Wang, K.; Zhi, Y.; Dong, Y. Gypenosides counteract hepatic steatosis and intestinal barrier injury in rats with metabolic associated fatty liver disease by modulating the adenosine monophosphate activated protein kinase and Toll-like receptor 4/nuclear factor kappa B pathways. Pharm. Biol., 2022, 60(1), 1949-1959.
[http://dx.doi.org/10.1080/13880209.2022.2126503] [PMID: 36205541]
[36]
Wang, Z.F.; Liu, J.; Yang, Y.A.; Zhu, H.L. A review: The anti-inflammatory, anticancer and antibacterial properties of four kinds of licorice flavonoids isolated from licorice. Curr. Med. Chem., 2020, 27(12), 1997-2011.
[http://dx.doi.org/10.2174/0929867325666181001104550] [PMID: 30277142]
[37]
Ashrafizadeh, M.; Zarrabi, A.; Orouei, S.; Kiavash Hushmandi; Hakimi, A.; Amirhossein Zabolian; Daneshi, S.; Samarghandian, S.; Baradaran, B.; Najafi, M. MicroRNA-mediated autophagy regulation in cancer therapy: The role in chemoresistance/chemosensitivity. Eur. J. Pharmacol., 2021, 892, 173660.
[http://dx.doi.org/10.1016/j.ejphar.2020.173660] [PMID: 33310181]
[38]
Hussen, B.M.; Hidayat, H.J.; Salihi, A.; Sabir, D.K.; Taheri, M.; Ghafouri-Fard, S. MicroRNA: A signature for cancer progression. Biomed. Pharmacother., 2021, 138, 111528.
[http://dx.doi.org/10.1016/j.biopha.2021.111528] [PMID: 33770669]
[39]
Han, M.; Gu, Y.; Lu, P.; Li, J.; Cao, H.; Li, X.; Qian, X.; Yu, C.; Yang, Y.; Yang, X.; Han, N.; Dou, D.; Hu, J.; Dong, H. Retracted Article: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation. Mol. Cancer, 2020, 19(1), 26.
[http://dx.doi.org/10.1186/s12943-020-1145-5] [PMID: 32020881]
[40]
Bao, L.; Li, X. MicroRNA-32 targeting PTEN enhances M2 macrophage polarization in the glioma microenvironment and further promotes the progression of glioma. Mol. Cell. Biochem., 2019, 460(1-2), 67-79.
[http://dx.doi.org/10.1007/s11010-019-03571-2] [PMID: 31218569]
[41]
Alizadeh, M.; Safarzadeh, A.; Beyranvand, F.; Ahmadpour, F.; Hajiasgharzadeh, K.; Baghbanzadeh, A.; Baradaran, B. The potential role of miR‐29 in health and cancer diagnosis, prognosis, and therapy. J. Cell. Physiol., 2019, 234(11), 19280-19297.
[http://dx.doi.org/10.1002/jcp.28607] [PMID: 30950056]
[42]
Cheng, C.; Yang, J.; Li, S.W.; Huang, G.; Li, C.; Min, W.P.; Sang, Y. HDAC4 promotes nasopharyngeal carcinoma progression and serves as a therapeutic target. Cell Death Dis., 2021, 12(2), 137.
[http://dx.doi.org/10.1038/s41419-021-03417-0] [PMID: 33542203]
[43]
Di Giorgio, E.; Hancock, W.W.; Brancolini, C. MEF2 and the tumorigenic process, hic sunt leones. Biochim. Biophys. Acta Rev. Cancer, 2018, 1870(2), 261-273.
[http://dx.doi.org/10.1016/j.bbcan.2018.05.007] [PMID: 29879430]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy