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Published on: March 30, 2019
Silymarin suppressed lung cancer growth in mice via inhibiting myeloid-derived suppressor cells
Tiancong Wu1, Wen Liu2, Wenjie Guo2
1Department of Radiation Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu Province, China.
Abstract:
In this study, we investigated the antitumor activity of Silymarin in a mouse model of colon cancer xenograft of Lewis lung cancer (LLC) cells. Silymarin significantly suppressed tumor growth and induced apoptosis of cells in tumor tissues at a dose of 25 and 50mg/kg. Silymarin treatment enhanced the infiltration and function of CD8(+) T cells. In the meantime, Silymarin decreased the level of IL-10 while elevated the level of IL-2 and IFN-γ in the serum of tumor-bearing mice. Finally, Silymarin reduced the proportion of myeloid-derived suppressor cells (MDSC) in the tumor tissue and also 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 were suppressed. 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.
Insights
Silymarin demonstrated significant antitumor effects against Lewis lung cancer (LLC) xenografts in mice. It suppressed tumor growth by enhancing CD8(+) T cell activity and reducing myeloid-derived suppressor cells (MDSC).
Area of Science:
- Immunology
- Cancer Research
- Pharmacology
Background:
- Lewis lung cancer (LLC) is a significant challenge in oncology.
- Understanding the immune microenvironment's role in tumor progression is crucial.
- Natural compounds like Silymarin are being explored for their therapeutic potential.
Purpose of the Study:
- To investigate the antitumor activity of Silymarin in a mouse model of colon cancer xenograft using Lewis lung cancer (LLC) cells.
- To elucidate the mechanisms underlying Silymarin's effects on the tumor microenvironment and immune response.
Main Methods:
- Establishment of a Lewis lung cancer (LLC) xenograft mouse model.
- Administration of Silymarin at doses of 25 and 50 mg/kg.
- Assessment of tumor growth, apoptosis, immune cell infiltration (CD8(+) T cells), cytokine levels (IL-10, IL-2, IFN-γ), and myeloid-derived suppressor cells (MDSC) markers (iNOS2, Arg-1, MMP9).
Main Results:
- Silymarin significantly suppressed LLC xenograft tumor growth and induced apoptosis.
- Silymarin enhanced CD8(+) T cell infiltration and function, increased IL-2 and IFN-γ levels, and decreased IL-10 levels.
- Silymarin reduced the proportion and function of myeloid-derived suppressor cells (MDSC) by downregulating iNOS2, Arg-1, and MMP9 mRNA expression.
Conclusions:
- Silymarin exhibits potent antitumor activity against LLC xenografts.
- The mechanism involves the inhibition of MDSC and promotion of CD8(+) T cell-mediated anti-tumor immunity.
- These findings support the potential of Silymarin as a therapeutic agent for lung cancer.
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