Acidic stress induces apoptosis and inhibits angiogenesis in human bone marrow‑derived endothelial progenitor cells

Huang,Shuai; He,Peiheng; Xu,Dongliang; Li,Jinglei; Peng,Xinsheng; Tang,Yubo

doi:10.3892/ol.2017.6947

Acidic stress induces apoptosis and inhibits angiogenesis in human bone marrow‑derived endothelial progenitor cells

Authors:
- Shuai Huang
- Peiheng He
- Dongliang Xu
- Jinglei Li
- Xinsheng Peng
- Yubo Tang
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Affiliations: Department of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Radiology, Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangzhou, Guangdong 510080, P.R. China, Department of Pharmacy, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China
Published online on: September 15, 2017 https://doi.org/10.3892/ol.2017.6947
Pages: 5695-5702
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Bone marrow‑derived endothelial progenitor cells (BM‑EPCs) are exposed to acidotic environments in a variety of physiological and pathological conditions, including in tumors. However, the effect of acidosis on the function of BM‑EPCs is still not fully understood. In the present study, BM‑EPCs were isolated and cultured at an extracellular pH (pHe) of 6.5 or pHe 7.4 in vitro prior to various experiments being performed. Cellular proliferation, migration and tube formation ability were detected by DNA content quantification, Transwell assay and Matrigel‑based angiogenesis assay. ELISA and western blot analysis measured protein secretion and expression, respectively. The results demonstrated that BM‑EPCs cultured at pHe 6.5 compared with at pHe 7.4 demonstrated: Induced apoptosis; inhibited cellular proliferation, migration and adhesion; markedly reduced vascular endothelial growth factor (VEGF) expression; and the capacity to incorporate into vascular networks. Acidic pHe 6.5 induced ratio expression of B‑cell lymphoma 2 (Bcl2)/Bcl2 associated X‑protein (Bax), which in turn induced apoptosis, and inhibited cellular proliferation and other functional activities, with involvement of activation of VEGF receptor 2, protein kinase B and p38 mitogen activated protein kinase. These observations raise the possibility that the acidic extracellular environment may perform an important role in the vasculogenesis of BM‑EPCs in tumor microenvironments. Therefore, culturing cancer cells at a lower pH that simulates endogenous tumor conditions may improve retention of the cellular heterogeneity identified in tumors.

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