Micro-particulate Ganoderma lucidum spore β-glucanin enhances the antitumor activity of gemcitabin via remodeling immunosuppressive microenvironment in Lewis lung cancer
10.16438/j.0513-4870.2021-0209
- VernacularTitle:微粒型灵芝孢子β-葡聚糖重塑免疫抑制微环境增强吉西他滨抗肺癌作用
- Author:
Fei-fei CHEN
1
,
2
;
Chang LI
1
,
2
;
Yi LUO
1
;
Meng-jia-li WEI
1
,
2
;
Qian MA
1
,
2
;
Jie SONG
1
,
2
;
Liang FENG
3
;
Xiao-bin JIA
3
;
Xiao-bin TAN
1
,
2
Author Information
1. Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China
2. Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing 210028, China
3. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China
- Publication Type:Research Article
- Keywords:
italic>Ganoderma lucidum spore;
italic>β-glucan;
gemcitabine;
tumor microenvironment;
tumor immunology
- From:
Acta Pharmaceutica Sinica
2021;56(7):1988-1998
- CountryChina
- Language:Chinese
-
Abstract:
Gemcitabine (GEM) is a commonly used drug in the clinical treatment of non-small cell lung cancer. Due to the accumulation of cells mediating immune escape and T cell depletion after chemotherapy, tumor microenvironment (TME) tends to be immunosuppressive status, which ultimately leads to tumor metastasis. The experimental protocol was approved by the Medical Laboratory Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine. Therefore, we observed the immunomodulatory effects of micro-particulate Ganoderma lucidum spore β-glucan (PGSG) on macrophages in vitro experiments. Next, mice subcutaneous Lewis lung cancer models were established to observe the anti-tumor effects of PGSG through oral administration of PGSG combined with GEM. Flow cytometry analysis was used to analyze the ratio of anti-tumor T cells in tumors and spleen, as well as the proportion of myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM) and regulatory cells (Tregs). The results showed that PGSG can up-regulate the expression of major histocompatibility antigens (MHC-II), CD40, CD86 and CD80 on the surface of macrophages, enhance the ability to phagocytosis of neutral red and further mediate the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4) and interleukin-10 (IL-10). In vivo experiments, combined administration can significantly decrease the volume and weight of tumors, reduce the ratio of MDSC (CD11b+Gr-1+), M-MDSC (CD11b+Ly6G-Ly6Chigh) and Treg (CD4+Foxp3+). At the same time, PGSG promoted the conversion of M2 (F4/80+CD206+) to M1 (F4/80+MHC-II+) and enhanced the response of helper T cell-1 (Th1) (CD4+IFN-γ+) and cytotoxic T lymphocyte (CTL) (CD8+IFN-γ+), which is of great significance for killing tumors. These results suggest that PGSG can regulate innate and adaptive antitumor immune responses, reshape the immunosuppressive microenvironment and enhance the anti-lung cancer effect of GEM.
