2.3 Effect on platelet-mediated angiogenesis
Platelets are considered to be the main actors in each step of
angiogenesis as they store various growth factors, proteases, cytokines,
chemokines and cell adhesion molecules (Patzelt et al., 2012;
Pipili-Synetos et al., 1998). Therefore, pharmacological interventions
of platelet-associated proangiogenic activity have been recognized as a
important adjuvant treatment for cancer (Bambace
et al., 2011; Radziwon-Balicka et
al., 2012).
The 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), a direct COX-1
product in platelet, can combine with other pro-angiogenic factors
released by platelets to regulate
angiogenesis
(Rauzi et al., 2016). Aspirin can block the angiogenic response of
thrombin-stimulated human platelets in human microvascular endothelial
cells (HMEC-1) (Etulain et al., 2013). In addition, aspirin inhibits
15(S)-HETE production in platelet with inhibition COX-1 to reduce
angiogenesis, which also provide a explanation for the protective
effects of low-dose aspirin on some cancers
(Rauzi et al., 2016) (Figure 2). A
study demonstrates that 15(S)-HETE can promote angiogenesis in HuDMECs
through the PI3K-Akt-mTOR-S6K1 signaling pathway (Zhang et al., 2005).
However, it warrants further study to verify the downstream of
15(S)-HETE signalling transduction when aspirin antiangiogenesis.
Platelet levels of thrombospondin-1 (TSP-1) have been indicated to
regulate early stage of tumor
angiogenesis (Zaslavsky et al.,
2010). In breast cancer patients, taking aspirin therapy can upregulate
TSP-1 level without a concurrent increase in VEGF levels in platelets
(Holmes et al., 2013). It is also indicated that pretreatment with
aspirin could reduce the amount of VEGF released from platelets at rest
and after being activated by ADP or interacting with MCF-7 cells
(Battinelli et al., 2011). Furthermore, aspirin may correct abnormal
platelet activation, prevent the release of a large number of
angiogenesis regulators, and then help normalize the tumor vasculature
and shape the tumor microenvironment, thereby reducing tumor invasion
and progression (Su et al., 2014). There is a registered clinical trial
to test the efficacy of aspirin use for exploring the platelet function
of its mechanism of action, such as the change levels of COX-1,
thrombospondin 1, NF-Kb and VEGF (Table1).