Diversified, endothelial cell-dependent cancer cell response to hypertensive serum modified by antihypertensive drugs

Recent studies have established a link between hypertension and an increased risk of cancer. The effects of antihypertensive treatment on cancer progression remain unclear. Objectives: Our study focused on whether serum from patients treated with antihypertensive drugs could decrease cancer-promoting properties of endothelial cells. We used cell lines, including endothelial cells (EAhy926) and various cancer cells, such as ovarian (SKOV-3), colorectal, pancreatic (PSN-1), breast (MCF-7), and lung cells. Serum was collected from hypertensive patients treated with amlodipine, nebivolol, and perindopril for 6 weeks, alongside samples from healthy individuals. Our findings indicate that the conditioned medium (CM) from EAhy926 cells exposed to hypertensive patient serum enhances cancer cell proliferation, migration, invasion, and adhesion. Notably, antihypertensive drugs, particularly nebivolol, were found to mitigate these effects significantly. Nebivolol-treated serum led to a reduction in cancer-promoting agents (like CXCL1, CXCL8, FGF5, tPA, TGF-β1, and VEGF) mRNA levels in cancer cells and increased expression of junctional proteins (E-cadherin, occludin, desmoglein) in endothelial cells. Additionally, these endothelial cells released fewer cancer-promoting proteins, including ANG1, CXCL1, CXCL12, EGF, TGF-β1, and VEGF. In summary, our study demonstrates that antihypertensive therapy, especially with nebivolol, potentially reverses hypertension-induced changes that exacerbate the cancer-promoting phenotype of endothelial cells. This suggests that beyond controlling blood pressure, antihypertensive treatments may also play a role in modulating cancer progression.