Aspirin suppresses components of lymphangiogenesis and lymphatic vessel remodeling by inhibiting the NF-B/VCAM-1 pathway in human lymphatic endothelial cells

作者：Prangsaengtong Orawin^*; Jantaree Phatcharida; Lirdprapamongkol Kriengsak; Ngiwsara Lukana; Svasti Jisnuson; Koizumi Keiichi

来源：Vascular Medicine, 2018, 23(3): 201-211.

DOI：10.1177/1358863X18760718

• anti-metastatic
• aspirin
• lymphangiogenesis
• NF-B
• VCAM-1

Lymphangiogenesis is the process of new vessel formation from pre-existing lymphatic vessels. The process mainly involves cell adhesion, migration, and tubule formation of lymphatic endothelial cells. Tumor-induced lymphangiogenesis is an important factor contributing to promotion of tumor growth and cancer metastasis via the lymphatic system. Finding the non-toxic agents that can prevent or inhibit lymphangiogenesis may lead to blocking of lymphatic metastasis. Recently, aspirin, a non-steroidal anti-inflammatory drug (NSAID), has been reported to inhibit in vivo lymphangiogenesis in tumor and incision wound models, but the mechanisms of actions of aspirin on anti-lymphangiogenesis have been less explored. In this study, we aim to explore the mechanism underlying the anti-lymphangiogenic effects of aspirin in primary human dermal lymphatic microvascular endothelial (HMVEC-dLy) cells in vitro. Pretreatment of aspirin at non-toxic dose 0.3 mM significantly suppressed in vitro cord formation, adhesion, and the migration abilities of the HMVEC-dLy cells. Western blotting analysis indicated that aspirin decreased expression of vascular cell adhesion molecule-1 (VCAM-1), at both protein and mRNA levels, and these correlated with the reduction of NF-B p65 phosphorylation. By using NF-B inhibitor (BAY-11-7085) and VCAM-1 siRNA, we showed that VCAM-1 expression is downstream of NF-B activation, and this NF-B/VCAM-1 signaling pathway controls cord formation, adhesion, and the migration abilities of the HMVEC-dLy cells. In summary, we demonstrate the potential of aspirin as an anti-lymphangiogenic agent, and elucidate its mechanism of action.

• 出版日期2018-6