3. Antiangiogenic effects of ASA combination with actual proven
therapies
The abnormal tumor vessels leads to inefficient delivery of drugs and
oxygen into tumors (Jain et al., 1998). Thus, the normalization of the
tumor vasculature by antiangiogenic drugs may reinforce other drugs
delivery to further solid tumors, thereby producing an enhancement
effect. As targeting angiogenesis is rising a great promise in patients
as an antitumor therapy in combination with
existing chemotherapies
(Ma et al., 2008), we analyze
antiangiogenesis properties of coadministration with aspirin.
The previous study has revealed that following coadministration with
aspirin therapy, VEGF levels decreased in women with breast cancer
relative to levels of receiving Tamoxifen therapy alone (Holmes et
al.,2013). Combination therapy of ASA drugs with a VEGF inhibitor block
angiogenesis more effectively than either agent alone (Huang et al.,
2016). In addition, the administration of aspirin as an adjuvant in
combination with Temozolomide, Bevacizumab and Sunitinib showed a
synergistic effect on reduce capillary-like tube length in comparison to
each exposure alone,in fact aspirin enhanced Temozolomide, Sunitinib and
Bevacizumab effect, decreasing significantly Glioblastoma-endothelial
cells VEGF-stimulated angiogenesis, especially at the high concentration
(Navone et al., 2018). Also, the expression of VEGFR-2, HIF-1α,
anti-apoptotic BCL-2 and PI3K/AKT suffered a reduction after combined
therapy of Temozolomide, Bevacizumab, Sunitinib and aspirin compared to
single-drug treatment (Navone et
al., 2018).
5-Fluorouracil (5-FU), a rationally synthesized antitumor agent, is
widely used to treat several common malignant tumors, including cancer
of the skin, colon and breast (Diasio et al., 1989). The expression of
VEGF-A and VEGF-C is significantly reduced in the tumors treated with
5-FU combination with aspirin, and the antitumor effect of 5-FU is
synergistically enhanced by aspirin (Zhang et al., 2013). There are
three registered clinical trials involved in evaluate the
antiangiogenesis efficacy of coadministation aspirin in treating cancers
(Table1).