Dai Xingbin, Jiang Pengjun, Ji Yanhua, Zhu Xuejun, Sun Xuemei
Department of Hematology, Affiliated Hospital of Nanjing University of Chinese Medicine Nanjing 210029, China.
First Clinical Medical College, Nanjing University of Chinese Medicine Nanjing 210029, China.
Am J Transl Res. 2019 Jun 15;11(6):3567-3577. eCollection 2019.
Studies have suggested trichosanthin (TCS) exerts antitumor activity mainly through direct cytotoxicity toward cancer cells and immune regulation. In this study, we conducted the proliferation and apoptosis assay on A20 cells and endothelial cells (ECs) with different concentrations of TCS and investigated the levels of gene expression linked to angiogenesis. Herein, a new mechanism that TCS inhibits murine B-cell lymphoma growth by anti-angiogenesis was reported. First, TCS inhibit tumor growth and prolonged survival significantly , and TCS depressed the formation of new blood vessels around the tumor in a dose-dependent manner. Further studies showed that the platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31)-positive endothelial cell numbers, and the serum levels of MMP-2 and MMP-9 were also lower in the study group than controls. However, TCS did neither change the ratio of T cells and NK cells in the spleen of treated mice nor affect the proliferation and apoptosis of A20 cells . Additionally, the newly formed blood vessels in chorioallantoic membranes treated with TCS were significantly reduced. Last, TCS may suppress the proliferation, induce apoptosis and decrease tube formation and migration of endothelial cells (ECs). And, the mRNA and protein levels of VEGF in ECs treated with TCS were lower than that in the control group. These findings confirm that inhibitory effect of TCS on A20 murine B-cell lymphoma growth is mediated via anti-angiogenesis, and which may be associated with the down-regulation of VEGF and MMPs expression. This is an indication that TCS may represent a natural anti-angiogenic drug for lymphoma therapy.
研究表明，天花粉蛋白（TCS）主要通过对癌细胞的直接细胞毒性和免疫调节发挥抗肿瘤活性。在本研究中，我们用不同浓度的TCS对A20细胞和内皮细胞（ECs）进行了增殖和凋亡检测，并研究了与血管生成相关的基因表达水平。在此，我们报道了一种新机制，即TCS通过抗血管生成抑制小鼠B细胞淋巴瘤生长。首先，TCS显著抑制肿瘤生长并延长生存期，且TCS以剂量依赖方式抑制肿瘤周围新血管的形成。进一步研究表明，研究组中血小板内皮细胞黏附分子-1（PECAM-1/CD31）阳性内皮细胞数量以及MMP-2和MMP-9的血清水平也低于对照组。然而，TCS既未改变治疗小鼠脾脏中T细胞和NK细胞的比例，也未影响A20细胞的增殖和凋亡。此外，用TCS处理的尿囊绒膜中的新形成血管显著减少。最后，TCS可能抑制内皮细胞（ECs）的增殖、诱导凋亡并减少其管腔形成和迁移。并且，用TCS处理的ECs中VEGF的mRNA和蛋白水平低于对照组。这些发现证实，TCS对A20小鼠B细胞淋巴瘤生长的抑制作用是通过抗血管生成介导的，这可能与VEGF和基质金属蛋白酶（MMPs）表达的下调有关。这表明TCS可能是一种用于淋巴瘤治疗的天然抗血管生成药物。
