|Table of Contents|

The anti-lung cancer mechanisms of Silymarin via inhibiting myeloid-derived suppressor cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2018 06
Page:
822-827
Research Field:
Publishing date:

Info

Title:
The anti-lung cancer mechanisms of Silymarin via inhibiting myeloid-derived suppressor cells
Author(s):
Wu Tiancong1Wang Xia2Zhu Xixu1
1.Department of Radiation Oncology,Nanjing General Hospital of Nanjing Command,PLA,Jiangsu Nanjing 210002,China;2.Department of Radiation Oncology,The Affiliated Jiangning Hospital of Nanjing Medical University,Jiangsu Nanjing 211100,China.
Keywords:
Silymarinlung cancerMDSCCD8+ T cell
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2018.06.003
Abstract:
Objective:To study the anti-lung cancer mechanisms of Silymarin via inhibiting myeloid-derived suppressor cells(MDSC).Methods:We developed a mouse xenograft model of Lewis lung cancer cells(LLC) in C57/BL6 mice and administered(i.g) Silymarin(25,50 mg/kg,once a day) dose dependently.Tumor volumes and mice body weight were measured.The expression of proliferating cell nuclear antigen(PCNA) related to tumor proliferation was detected by immunohistochemistry(IHC) staining.The apoptosis of LLC cells was detected by TUNEL staining.Tumor-infiltrating CD8+ T cells in LLC xenografts were detected by IHC staining.The percentage of CD11b+Gr-1+ MDSC was detected by flow cytometry.RNA was extracted from tumor tissue of mice and the expressions of Arg-1,iNOS2 and MMP9 mRNA were determined by Q-PCR.Results:Silymarin significantly suppressed tumor growth and induced apoptosis of cells in tumor tissues at a dose of 25 and 50 mg/kg.Silymarin treatment enhanced the infiltration and function of CD8+ T cells.Finally,Silymarin reduced the proportion of myeloid-derived suppressor cells(MDSC) in the tumor tissue and the mRNA expressions of inducible nitric oxide synthases-2(iNOS2),arginase-1(Arg-1) and MMP9,which indicated that the function of MDSC in tumor tissues was suppressed.Conclusion:Altogether,our data here showed that Silymarin inhibited the MDSC and promoted the infiltration and function of CD8+ T cells thus suppressed the growth of LLC xenografts,which provides evidence for the possible use of Silymarin against lung cancer.

References:

[1]Siegel RL,Miller KD,Jemal A.Cancer statistics,2015[J].CA Cancer J Clin,2015,65(1):5-29.
[2]Landi L,Cappuzzo F.Experience with erlotinib in the treatment of non-small cell lung cancer[J].Ther Adv Respir Dis,2015,9(4):146-163.
[3]Minguet J,Smith KH,Bramlage P.Targeted therapies for treatment of non-small cell lung cancer—Recent advances and future perspectives[J].Int J Cancer,2016,138(11):2549-2561.
[4]Schiller GJ,O'Brien SM,Pigneux A,et al.Single-agent laromustine,a novel alkylating agent,has significant activity in older patients with previously untreated poor-risk acute myeloid leukemia[J].J Clin Oncol,2010,28(5):815-821.
[5]Sharma SV,Bell DW,Settleman J,et al.Epidermal growth factor receptor mutations in lung cancer[J].Nat Rev Cancer,2007,7(3):169-181.
[6]Perez-Soler R,Chachoua A,Hammond LA,et al.Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer[J].J Clin Oncol,2004,22(16):3238-3247.
[7]Remon J,Moran T,Majem M,et al.Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer:A new era begins[J].Cancer Treat Rev,2014,40(1):93-101.
[8]Hegedus C,Truta-Feles K,Antalffy G,et al.Interaction of the EGFR inhibitors gefitinib,vandetanib,pelitinib and neratinib with the ABCG2 multidrug transporter:Implications for the emergence and reversal of cancer drug resistance[J].Biochem Pharmacol,2012,84(3):260-267.
[9]Abenavoli L,Capasso R,Milic N,et al.Milk thistle in liver diseases:Past,present,future[J].Phytother Res,2010,24(10):1423-1432.
[10]Hackett ES,Twedt DC,Gustafson DL.Milk thistle and its derivative compounds:A review of opportunities for treatment of liver disease[J].J Vet Intern Med,2013,27(1):10-16.
[11]Tzeng JI,Chen MF,Chung HH,et al.Silymarin decreases connective tissue growth factor to improve liver fibrosis in rats treated with carbon tetrachloride[J].Phytother Res,2013,27(7):1023-1028.
[12]Li W,Mu D,Song L,et al.Molecular mechanism of silymarin-induced apoptosis in a highly metastatic lung cancer cell line anip973[J].Cancer Biother Radiopharm,2011,26(3):317-324.
[13]Kremer M,Suezer Y,Volz A,et al.Critical role of perforin-dependent CD8+ T cell immunity for rapid protective vaccination in a murine model for human smallpox[J].PLoS Pathog,2012,8(3):e1002557.
[14]Gerloni M,Zanetti M.CD4 T cells in tumor immunity[J].Springer Semin Immunopathol,2005,27(1):37-48.
[15]Meyer C,Sevko A,Ramacher M,et al.Chronic inflammation promotes myeloid-derived suppressor cell activation blocking antitumor immunity in transgenic mouse melanoma model[J].Proc Natl Acad Sci USA,2011,108(41):17111-17116.
[16]Ostrand-Rosenberg S,Sinha P.Myeloid-derived suppressor cells:Linking inflammation and cancer[J].J Immunol,2009,182(8):4499-4506.
[17]Mazzoni A,Bronte V,Visintin A,et al.Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism[J].J Immunol,2002,168(2):689-695.
[18]Chauvin JM,Pagliano O,Fourcade J,et al.TIGIT and PD-1 impair tumor antigen-specific CD8(+) T cells in melanoma patients[J].J Clin Invest,2015,125(5):2046-2058.
[19]Kuss I,Hathaway B,Ferris RL,et al.Decreased absolute counts of T lymphocyte subsets and their relation to disease in squamous cell carcinoma of the head and neck[J].Clin Cancer Res,2004,10(11):3755-3762.
[20]Intlekofer AM,Thompson CB.At the bench:Preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy[J].J Leukoc Biol,2013,94(1):25-39.
[21]Shanker A,Verdeil G,Buferne M,et al.CD8 T cell help for innate antitumor immunity[J].J Immunol,2007,179(10):6651-6662.
[22]Tateyama M,Oyaizu N,McCloskey TW,et al.CD4 T lymphocytes are primed to express Fas ligand by CD4 cross-linking and to contribute to CD8 T-cell apoptosis via Fas/FasL death signaling pathway[J].Blood,2000,96(1):195-202.
[23]Filaci G,Suciu-Foca N.CD8+ T suppressor cells are back to the game:Are they players in autoimmunity[J]? Autoimmun Rev,2002,1(5):279-283.
[24]Kaplan DH,Shankaran V,Dighe AS,et al.Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice[J].Proc Natl Acad Sci USA,1998,95(13):7556-7561.
[25]Afshar-Sterle S,Zotos D,Bernard NJ,et al.Fas ligand-mediated immune surveillance by T cells is essential for the control of spontaneous B cell lymphomas[J].Nat Med,2014,20(3):283-290.

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Last Update: 2018-01-29