BACKGROUND & AIMS:
:Maslinic acid is found in various natural sources, most notably in pomace olive oil, and exerts pro-apoptotic activities in various cancer cells in vitro. In the present study, DU145 human prostate cancer cells were cultured with 0-25 μm-maslinic acid to examine the effects of maslinic acid on the metastatic capacity of prostate cancer cells. Maslinic acid significantly (P <0.05) inhibited the basal and epidermal growth factor (EGF)-induced migration (27-64 %), invasion (23-60 %) and adhesion (8-40 %) of DU145 cells. Maslinic acid significantly (P <0·05) down-regulated both basal and EGF-stimulated secretion of matrix metalloproteinase (MMP)-9 (25-67 %), MMP-2 (50-86 %), urokinase-type plasminogen activator (uPA, about 100 %), vascular endothelial growth factor (VEGF, 98-100 %) and tissue inhibitors of metalloproteinases (TIMP)-1, as well as expression of uPA receptor (uPAR), intercellular adhesion molecules (22-33 %), vascular cell adhesion molecules (23-46 %) and E-cadherin, whereas it increased TIMP-2 secretion. Maslinic acid dramatically reduced the levels of hypoxia-inducible factor-1α (HIF-1α) protein and mRNA; the reduction was accompanied by reduced stability, nuclear levels and transcriptional activity of HIF-1α. The levels of phospho-Akt and phospho-extracellular signal-related kinase (ERK) were reduced in cells treated with maslinic acid, and the phosphoinositide 3-kinase inhibitor LY294002 and the mitogen-activated protein kinase kinase inhibitor PD98059 reduced HIF-1α levels and VEGF secretion. The results show that maslinic acid markedly inhibited the migration, invasion and adhesion of DU145 prostate cancer cells. Suppressing HIF-1α activation by inhibiting Akt and ERK activation may be part of the mechanism by which maslinic acid inhibited uPAR, E-cadherin, VEGF and MMP expression in DU145 cells.
背景与目标:
: Maslinic酸存在于各种天然来源中,最显着的是果渣橄榄油中,并在体外在各种癌细胞中发挥促凋亡活性。在本研究中,用0-25μm-maslinic酸培养DU145人前列腺癌细胞,以检查maslinic酸对前列腺癌细胞转移能力的影响。大西林酸显著 (P <0.05) 抑制基底和表皮生长因子 (EGF) 诱导的DU145细胞迁移 (27-64%) 、侵袭 (23-60%) 和粘附 (8-40%)。山麦酸显著 (P & lt; 0.05) 下调基质金属蛋白酶-9 (25-67%) 、MMP-2 (50-86%) 、尿激酶型纤溶酶原激活物 (uPA,约100%) 、血管内皮生长因子 (VEGF,98-100%) 和金属蛋白酶 (TIMP)-1的组织抑制剂,以及uPA受体 (uPAR),细胞间粘附分子 (22-33%),血管细胞粘附分子 (23-46%) 和E-钙粘蛋白的表达,而它增加了TIMP-2分泌。Maslinic酸显着降低了缺氧诱导因子-1α (HIF-1α) 蛋白和mRNA的水平; 降低伴随着HIF-1α 的稳定性,核水平和转录活性降低。在用山糖酸处理的细胞中,磷酸-Akt和磷酸-细胞外信号相关激酶 (ERK) 的水平降低,磷酸肌醇3-激酶抑制剂LY294002和丝裂原活化蛋白激酶抑制剂PD98059降低了HIF-1α 水平和VEGF分泌。结果表明,大西林酸可明显抑制DU145前列腺癌细胞的迁移、侵袭和粘附。通过抑制Akt和ERK激活来抑制HIF-1α 激活可能是maslinic酸抑制DU145细胞中uPAR,E-cadherin,VEGF和MMP表达的部分机制。