Angiogenesis and vasculogenic mimicry are inhibited by 8-Br-cAMP through activation of the cAMP/PKA pathway in colorectal cancer

OncoTargets and Therapy
Sen WangYueming Sun

Abstract

Vasculogenic mimicry (VM) describes the formation of an epithelial-independent tumor microcirculation system that differs from traditional angiogenesis. Angiogenesis and the formation of VM are closely related through the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway and the epithelial-mesenchymal transition (EMT) process. In this study, 8-Br-cAMP, a cAMP analog and PKA activator, was used to activate the cAMP/PKA pathway to evaluate the effects of cAMP/PKA on angiogenesis and VM in colorectal cancer (CRC) cells. We used a syngeneic model of CRC in BALB/c mice. We discovered that treatment with 8-Br-cAMP significantly reduced tumor number compared to control mice after the 7th, 14th, and 28th days of treatment. VM was evaluated by periodic acid-schiff (PAS)-CD31 staining, and we found that VM was inhibited by 8-Br-cAMP treatment in vivo. Immunohistochemistry confirmed the inhibition of vascular endothelial growth factor (VEGF) and cAMP and the activation of PKA by 8-Br-cAMP; quantitative real-time-PCR (qRT-PCR) demonstrated that 8-Br-cAMP regulated the expression of vascular endothelial (VE)-cadherin, matrix metalloproteinase 2 (MMP2), ephrin type-A receptor 2 (EphA2), and VEGF in vivo. Experiments in vit...Continue Reading

Citations

Feb 28, 2020·World Journal of Gastrointestinal Oncology·Wen-Qi CuiLi-Xuan Sang
May 20, 2020·Molecular Biology Reports·Nazila Fathi MaroufiMohammad Nouri
Aug 16, 2018·International Urology and Nephrology·Ke SunChanglin Mei
Jan 1, 2021·Cancers·Chang-Xu ChenJean X Jiang
Jun 8, 2021·Cancer Biomarkers : Section a of Disease Markers·Ganbiao WangYongxiang Li
Jul 4, 2021·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·M WuP Li

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Methods Mentioned

BETA
electrophoresis

Software Mentioned

Primer3

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