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.
[http://dx.doi.org/10.1007/s11912-019-0820-4] [PMID: 31236716]
[http://dx.doi.org/10.1016/S0140-6736(20)31288-5] [PMID: 32861308]
[http://dx.doi.org/10.1007/s11864-020-00774-4] [PMID: 32725377]
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[http://dx.doi.org/10.1186/s12199-018-0740-1] [PMID: 30340457]
[http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2018026839] [PMID: 30317974]
[http://dx.doi.org/10.1007/978-3-030-15138-6_13] [PMID: 31123895]
[http://dx.doi.org/10.1002/cam4.2108] [PMID: 30945475]
[http://dx.doi.org/10.1016/j.biopha.2019.109570] [PMID: 31710893]
[http://dx.doi.org/10.1155/2020/2018162] [PMID: 32382534]
[http://dx.doi.org/10.1016/j.biopha.2020.110440] [PMID: 32768942]
[http://dx.doi.org/10.1155/2017/2613198] [PMID: 28299321]
[http://dx.doi.org/10.1016/j.csbj.2020.05.004] [PMID: 32489526]
[http://dx.doi.org/10.1080/13880209.2019.1626449] [PMID: 31401919]
[PMID: 23841271]
[http://dx.doi.org/10.1142/S0192415X19500873] [PMID: 31801358]
[http://dx.doi.org/10.2147/CMAR.S269991] [PMID: 33173345]
[http://dx.doi.org/10.3892/or.2015.3919] [PMID: 25901555]
[http://dx.doi.org/10.1093/jpp/rgac018] [PMID: 35596792]
[http://dx.doi.org/10.1016/j.ijbiomac.2022.02.119] [PMID: 35218798]
[http://dx.doi.org/10.1016/j.jmoldx.2013.05.007] [PMID: 23810501]
[http://dx.doi.org/10.1016/j.molcel.2019.10.023] [PMID: 31735641]
[http://dx.doi.org/10.3389/fonc.2019.00421] [PMID: 31192126]
[http://dx.doi.org/10.1158/0008-5472.CAN-17-3841] [PMID: 29880482]
[http://dx.doi.org/10.1186/s13045-015-0231-4] [PMID: 26851944]
[http://dx.doi.org/10.2147/OTT.S216355] [PMID: 31695427]
[http://dx.doi.org/10.1016/j.biopha.2017.04.001] [PMID: 28415048]
[http://dx.doi.org/10.2147/DDDT.S181939] [PMID: 30510404]
[http://dx.doi.org/10.1186/s13046-021-01995-7] [PMID: 34108030]
[http://dx.doi.org/10.1021/acsomega.2c06451] [PMID: 36816691]
[http://dx.doi.org/10.1002/ptr.3443] [PMID: 21394806]
[http://dx.doi.org/10.1016/j.biopha.2020.110917] [PMID: 33217688]
[http://dx.doi.org/10.1080/14786419.2020.1786825] [PMID: 32744101]
[http://dx.doi.org/10.1016/j.jpba.2020.113839] [PMID: 33388645]
[http://dx.doi.org/10.1080/13880209.2022.2126503] [PMID: 36205541]
[http://dx.doi.org/10.2174/0929867325666181001104550] [PMID: 30277142]
[http://dx.doi.org/10.1016/j.ejphar.2020.173660] [PMID: 33310181]
[http://dx.doi.org/10.1016/j.biopha.2021.111528] [PMID: 33770669]
[http://dx.doi.org/10.1186/s12943-020-1145-5] [PMID: 32020881]
[http://dx.doi.org/10.1007/s11010-019-03571-2] [PMID: 31218569]
[http://dx.doi.org/10.1002/jcp.28607] [PMID: 30950056]
[http://dx.doi.org/10.1038/s41419-021-03417-0] [PMID: 33542203]
[http://dx.doi.org/10.1016/j.bbcan.2018.05.007] [PMID: 29879430]