Li Chunyu, Wang Qi, Shen Shen, Wei Xiaolu, Li Guoxia
Department of Integrated Chinese Traditional and Western Medicine, International Medical School, Tianjin Medical University, Tianjin 300070, P.R. China.
Department of Oncology, Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai 200433, P.R. China.
Oncol Lett. 2018 Aug;16(2):2289-2298. doi: 10.3892/ol.2018.8943. Epub 2018 Jun 11.
Metastasis is the primary cause of mortality in patients with breast cancer and lacks effective therapeutic agents. Oridonin, an active diterpenoid compound isolated from , was identified to be the most potent anti-tumor ingredient. However, the molecular mechanisms responsible for its anti-metastatic effects remain unclear. In the present study, oridonin significantly suppressed the migration, invasion and adhesion of MDA-MB-231 and 4T1 breast cancer cells, and inhibited tube formation of human umbilical vein endothelial cells in a dose-dependent manner. The expression levels of epithelial-mesenchymal transition (EMT)-associated marker and the hypoxia inducible factor 1α (HIF-1α)/vascular endothelium growth factor (VEGF) signaling pathway mRNA and proteins were determined by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively . The results demonstrated that oridonin effectively inhibited EMT as demonstrated by the significant increases in the expression levels of E-cadherin, and decreased expression of N-cadherin, Vimentin and Snail. In addition, oridonin exerted its anti-angiogenesis activity through significantly decreasing HIF-1α, VEGF-A and VEGF receptor-2 protein expression. Furthermore, oridonin was demonstrated to decrease the micro-vessel density as evidenced by the decreased expression of cluster of differentiation 31, a marker for neovasculature. In brief, oridonin inhibits tumor cell migration, invasion and adhesion, as well as tumor angiogenesis, which are mediated by suppressing EMT and the HIF-1α/VEGF signaling pathway. The results of the present study suggest that oridonin may be a promising anti-metastatic agent in breast cancer treatment.
转移是乳腺癌患者死亡的主要原因，且缺乏有效的治疗药物。冬凌草甲素是一种从[植物名称未给出]中分离出的活性二萜类化合物，被确定为最有效的抗肿瘤成分。然而，其抗转移作用的分子机制仍不清楚。在本研究中，冬凌草甲素显著抑制MDA-MB-231和4T1乳腺癌细胞的迁移、侵袭和黏附，并以剂量依赖的方式抑制人脐静脉内皮细胞的管腔形成。分别通过逆转录-定量聚合酶链反应和蛋白质印迹法测定上皮-间质转化（EMT）相关标志物以及缺氧诱导因子1α（HIF-1α）/血管内皮生长因子（VEGF）信号通路mRNA和蛋白质的表达水平。结果表明，冬凌草甲素有效抑制EMT，表现为E-钙黏蛋白表达水平显著增加，而N-钙黏蛋白、波形蛋白和Snail的表达降低。此外，冬凌草甲素通过显著降低HIF-1α、VEGF-A和VEGF受体-2蛋白表达发挥其抗血管生成活性。此外，冬凌草甲素被证明可降低微血管密度，这可通过新生血管标志物分化簇31表达的降低来证明。简而言之，冬凌草甲素抑制肿瘤细胞的迁移、侵袭和黏附以及肿瘤血管生成，这是通过抑制EMT和HIF-1α/VEGF信号通路介导的。本研究结果表明，冬凌草甲素可能是一种有前途的用于乳腺癌治疗的抗转移药物。
