Department of Pharmaceutical Engineering, College of Life Science and Biotechnology, Heilongjiang August First Land Reclamation University, Daqing High-Tech Industrial Development Zone, P.R. China.
Can J Physiol Pharmacol. 2011 Sep;89(9):665-73. doi: 10.1139/y11-058. Epub 2011 Aug 18.
Diosmetin (DGVL) extracted from the traditional Chinese herb Galium verum L. has been found to have anticancer activity. In this study, the effects of DGVL on the thymus of U14-bearing mice were investigated. Using flow cytometry, peripheral blood lymphocytes were characterized based on the expression of surface markers for T helper cells (CD4(+)) and T suppressor cells (CD8(+)). Serum levels of tumor necrosis factor α (TNF-α), interleukin-2 (IL-2), IL-10, and transforming growth factor β1 (TGF-β1) and a cell proliferation assay were determined with an enzyme-linked immunosorbent assay. The expression of Fas and Fas ligand (FasL) on the thymus was determined by Western blotting. Our results showed that DGVL inhibited tumor growth and significantly increased the thymus weight compared with the control. Also, DGVL elevated serum levels of IL-2 and significantly reduced levels of TNF-α, TGF-β1, and IL-10 in a dose-dependent manner. Histological study and terminal dUTP nick end labeling staining results showed that DGVL protected thymus tissue against the onslaught of tumor growth by inhibiting thymus lymphocyte apoptosis. The cell proliferation assay revealed that DGVL might promote more thymus lymphocytes towards proliferation. Furthermore, the ratio of CD4(+)/CD8(+) T lymphocytes was significantly increased from 0.69 to 2.29 by treatment with DGVL. Immunoblotting analyses revealed that the expression of Fas and FasL on the thymus was lower in mice in the DGVL treatment group than in the control mice. In conclusion, DGVL can inhibit tumor growth and protect tumor-induced apoptosis of the thymus, and the mechanism is closely associated with reduced cell death in the thymus and a Fas-FasL-dependent pathway.
地牡宁（DGVL）从传统的中药拉拉藤中提取，已被发现具有抗癌活性。在这项研究中，研究了 DGVL 对荷瘤 U14 小鼠胸腺的影响。采用流式细胞术，根据 T 辅助细胞（CD4(+））和 T 抑制细胞（CD8(+））表面标志物的表达，对外周血淋巴细胞进行了特征描述。采用酶联免疫吸附试验测定肿瘤坏死因子α（TNF-α）、白细胞介素-2（IL-2）、IL-10 和转化生长因子β1（TGF-β1）的血清水平和细胞增殖试验。采用 Western 印迹法测定胸腺上 Fas 和 Fas 配体（FasL）的表达。结果表明，DGVL 抑制肿瘤生长，与对照组相比，胸腺重量明显增加。此外，DGVL 呈剂量依赖性地升高血清中 IL-2 的水平，并显著降低 TNF-α、TGF-β1 和 IL-10 的水平。组织学研究和末端 dUTP 缺口末端标记染色结果表明，DGVL 通过抑制胸腺淋巴细胞凋亡来保护胸腺组织免受肿瘤生长的侵袭。细胞增殖试验表明，DGVL 可能促进更多的胸腺淋巴细胞增殖。此外，DGVL 治疗组 CD4(+)/CD8(+)T 淋巴细胞的比值从 0.69 显著增加到 2.29。免疫印迹分析表明，DGVL 处理组小鼠胸腺上 Fas 和 FasL 的表达低于对照组。总之，DGVL 可抑制肿瘤生长，保护肿瘤诱导的胸腺细胞凋亡，其机制与减少胸腺细胞死亡和 Fas-FasL 依赖性途径密切相关。
