The purpose of this study was to investigate whether matrine can affect the phenotypes and functional maturation of dendritic cells (DC), and to secrete many cytokines, as well as the cytotoxic T lymophocyte (CTL) specific killing effect induced by gastric carcinoma dendritic cells vaccine in vitro.
Materials and methods
The experimental groups consisted of three concentrations of matrine (0.5, 1.0, and 2.0 mg/mL). The DC maturation was detected by flow cytometry. The proliferation of T cells was detected by cell counting kit-8 (CCK-8) method. The secretions of cytokines by CTLs were detected by enzyme-linked immunosorbent assay (ELISA). The specific killing capacity of CTLs to target MKN45 gastric cancer cells was detected by lactate dehydrogenase (LDH) release assay.
Results
The results showed that matrine could increase the expressions of CD86 and CD83 in a dose-dependent manner. Matrine could promote T cell proliferation (P<0.05). Moreover, matrine also significantly increased the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-12p70 (IL-12p70), respectively (P<0.05). The therapeutic vaccination with DCs vaccine treated with lipopolysaccharide (LPS) plus matrine resulted in improved killing effect as compared to that observed with DCs treated with LPS alone (P<0.05).
Conclusion
These findings define matrine as an immune adjuvant that enhances the DC activation and demonstrate a new pharmacological approach to improve the therapeutic effect of autogenous DC vaccines.
BartonG.M., MedzhitovR.Control of adaptive immune responses by Toll-like receptors. Curr Opin Immunol.14 (2002) 380–383.
2.
PaluckaK.KUenoH., G Zurawski, . Building on dendritic cell subsets to improve cancer vaccines. Curr Opin Immunol.22 (2010) 258–263.
3.
KimJ.H., KangT.H., NohK.H., . Enhancement of dendritic cell-based vaccine potency by anti-apoptotic siRNAs targeting key pro-apoptotic proteins in cytotoxic CD8(+) T cell-mediated cell death. Immunol Lett. 122 (2009) 58–67.
4.
KimJ.H., KangT.H., NohK.H., . Enhancement of DC vaccine potency by activating the PI3K/AKT pathway with a small interfering RNA targeting PTEN, Immunol Lett.134 (2010) 47–54.
5.
KangT.H., BaeH.C., S, H. Kim, . Modification of dendritic cells with interferon-gammainducible protein-10 gene to enhance vaccine potency. J Gene Med. 11 (2009) 889–898.
6.
OkadaN., N Mori, R Koretomo, . Augmentation of the migratory ability of DC-based vaccine into regional lymph nodes by efficient CCR7 gene transduction. Gene Ther. 12 (2005) 129–139.
7.
JyL., J.Y. L., ZhangF.C.The immunoregulatory effects of Chinese herbal medicine on the maturation and function of dendritic cells. J Ethnopharmacol.171 (2015) 184–195.
8.
ZhangJ.L.F., LiJ.The immunoregulatory effects of traditional Chinese medicine on treatment of asthma or asthmatic inflammation. Am J Chin Med.43 (2015) 1059–1081.
9.
HeYXZhangYYZhouYQ. Effect of Acupuncture Stimulation on Improving the Immunity of Synovial Tissue in Rheumatoid Joints via MAPK Pathway. Acupunct Electrother Res. DOI: https://doi.org/10.3727/036012921X16287835103462.
10.
J.W., G. H., DongY., . Matrine induces Akt/mTOR signalling inhibition-mediated autophagy and apoptosis in acute myeloid leukaemia cells. J Cell Mol Med. 21 (2017) 1171–1181.
11.
HuZChenBTongJHuangDLuS.The change of C-fos expression in ovariectomized rats following electroacupuncture treatment–an immunohistochemistry study. Acupunct Electrother Res.1993;18(2)117-24.
12.
Y.Y. G., ChenM.H., MayB.H., . Matrine induces apoptosis in multiple colorectal cancer cell lines in vitro and inhibits tumour growth with minimum side effects in vivo via Bcl-2 and caspase-3. Phytomedicine. 51 (2018) 214–225.
13.
GuoS., ChenY., C Pang, . Matrine is a novel inhibitor of the TMEM16A chloride channel with anti lung adenocarcinoma effects. J Cell Physiol. 234 (2019) 8698–8708.
14.
BrayF., FerlayJ., SoerjomataramI., . Global Cancer Statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68 (2018) 394–424.
15.
JinH., SunJ., ZhuK., . The prognostic value of neutrophil lymphocyte ratio is superior to derived neutrophil-lymphocyte ratio in advanced gastric cancer treated with preoperative chemotherapy and sequential R0 resection: a 5-year follow-up. Onco Targets Ther. 10 (2017) 2655–2664.
16.
LiC., LiangS.J., ZhangC.L.,. Allogenic dendritic cell and tumor cell fused vaccine for targeted imaging and enhanced immunotherapeutic efficacy of gastric cancer. Biomaterials. 54 (2015)177-187.
17.
GoldingerS.M., DummerR., BaumgaertnerP., . Nano-particle vaccination combined with TLR-7 and-9 ligands triggers memory and effector CD8(+) T-cell responses in melanomapatients. Eur J Immunol. 42 (2012) 3049–3061.
18.
DangY., WagnerW.M., GadE., . Dendritic cell-activating vaccine adjuvants differ in the ability to elicit antitumor immunity due to an adjuvant-specific induction of immunosuppressive cells. Clin Cancer Res. 18 (2012) 3122–3131.
19.
LeeA.W., TruongT., BickhamK., . A clinical grade cocktail of cytokines and PGE2 results in uniform maturation of human monocyte-derived dendritic cells:implications for immunotherapy. Vaccine. 4 (2002) A8-A22.
LintS.V., WilgenhofS., HeirmanC., . Optimized dendritic cell-based immunotherapy for melanoma: the trimix-formula. Cancer Immunol Immunother. 63 (2014) 959–967.
22.
OhnoY., KitamuraH., TakahashiN., . IL-6 down-regulates HLA class II expression and IL-12 production of human dendritic cells to impair activation of antigen-specific CD4+ T cells. Cancer Immunol Immunother. 65 (2016) 193–204.
23.
DoornE.V.ELiuH., HuckriedeA., . Safety and tolerability evaluation of the use of Montanide ISATM51 as vaccine adjuvant:a systematic review. Hum Vaccin Immunotherapeut. 12 (2016) 159–169.
LasekW., R. Zagożdżon, JakobisiakM.Interleukin 12:Still a promising candidate for tumor immunotherapy? Cancer Immunol Immunother. 63(2014)419–435.
26.
BlancoP., PaluckaA.K., PascualV., . Dendritic cells and cytokines in human inflammatory and autoimmune diseases. Cytokine Growth Factor Rev. 19 (2008) 41–52.
27.
OleszyckaE., LavelleE.C.Immunomodulatory properties of the vaccine adjuvant alum. Curr Opin Immunol.28 (2014) 1–5.
28.
LevineB., DereticV.Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol.7 (2007) 767–777.
29.
WuD., ShaoK., ZhouQ., . Autophagy and Ubiquitin-Mediated Proteolytic Degradation of PML/Rarα Fusion Protein in Matrine-Induced Differentiation Sensitivity Recovery of ATRA-Resistant APL (NB4-LR1) Cells:in Vitro and in Vivo Studies. Cell Physiol Biochem. 48 (2018) 2286–2301.
30.
MaK., HuangM.Y., GuoY.X., . Matrine-induced autophagy counteracts cell apoptosis via the ERK signaling pathway in osteosarcoma cells, Oncol Lett. 12 (2016) 1854-1860.
31.
YangJ., YaoS.JNK-Bcl-2/Bcl-xL-Bax/Ba. Pathway Mediates the Crosstalk between Matrine-Induced Autophagy and Apoptosis via Interplay with Beclin 1. Int J Mol Sci.16 (2015) 25744–25758.
32.
XieS.B., HeX.X., YaoS.K.Matrine-induced autophagy regulated by p53 through AMP-activated protein kinase in human hepatoma cells, Int J Oncol. 47 (2015) 517–526.
33.
BrossartP., WirthsS., StuhlerG., . Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptidepulsed dendritic cells. Blood. 96 (2000) 3102–3108.
