Molecular Oncology, Basil Hetzel Institute, Queen Elizabeth Hospital, Woodville South, SA 5011, Australia.
Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia.
Int J Mol Sci. 2018 Feb 26;19(3):653. doi: 10.3390/ijms19030653.
Expression of aquaporin-1 (AQP1) in endothelial cells is critical for their migration and angiogenesis in cancer. We tested the AQP1 inhibitor, bacopaside II, derived from medicinal plant , on endothelial cell migration and tube-formation in vitro using mouse endothelial cell lines (2H11 and 3B11) and human umbilical vein endothelial cells (HUVEC). The effect of bacopaside II on viability, apoptosis, migration and tubulogenesis was assessed by a proliferation assay, annexin-V/propidium iodide flow cytometry, the scratch wound assay and endothelial tube-formation, respectively. Cell viability was reduced significantly for 2H11 at 15 μM ( = 0.037), 3B11 at 12.5 μM ( = 0.017) and HUVEC at 10 μM ( < 0.0001). At 15 μM, the reduced viability was accompanied by an increase in apoptosis of 38%, 50% and 32% for 2H11, 3B11 and HUVEC, respectively. Bacopaside II at ≥10 μM significantly reduced migration of 2H11 ( = 0.0002) and 3B11 ( = 0.034). HUVECs were most sensitive with a significant reduction at ≥7.5 μM ( = 0.037). Tube-formation was reduced with a 15 μM dose for all cell lines and 10 μM for 3B11 ( < 0.0001). These results suggest that bacopaside II is a potential anti-angiogenic agent.
水通道蛋白-1（AQP1）在血管内皮细胞中的表达对于其在癌症中的迁移和血管生成至关重要。我们在体外使用小鼠内皮细胞系（2H11 和 3B11）和人脐静脉内皮细胞（HUVEC）测试了来源于药用植物的水通道蛋白-1 抑制剂巴卡丁 II 对内皮细胞迁移和管状形成的影响。通过增殖测定、膜联蛋白-V/碘化丙啶流式细胞术、划痕实验和内皮管状形成分别评估了巴卡丁 II 对活力、凋亡、迁移和管状形成的影响。2H11 在 15 μM（ = 0.037）、3B11 在 12.5 μM（ = 0.017）和 HUVEC 在 10 μM（ < 0.0001）时，细胞活力显著降低。在 15 μM 时，减少的活力伴随着凋亡的增加，2H11、3B11 和 HUVEC 分别增加 38%、50%和 32%。巴卡丁 II ≥10 μM 显著降低了 2H11（ = 0.0002）和 3B11（ = 0.034）的迁移。HUVEC 最敏感，≥7.5 μM 时显著降低（ = 0.037）。所有细胞系的管形成在 15 μM 剂量下减少，3B11 在 10 μM 剂量下减少（ < 0.0001）。这些结果表明，巴卡丁 II 是一种有潜力的抗血管生成剂。
