Abstract
The aim of this study is to evaluate whether the administration of renin-angiotensin system (RAS) inhibitors, angiotensin-I converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), is associated with treatment outcome in patients with esophageal squamous cell carcinoma. A total of 141 esophageal squamous cell carcinoma patients receiving esophagectomy were identified, and were divided into two groups: an ACEI/ARB group (n=20), and a non-ACEI/ARB group (n=121). The effect of ACEIs or ARBs on cell proliferation and vascular endothelial growth factor (VEGF) secretion of esophageal squamous cell carcinoma cell lines, CE81T/VGH and TE2, were investigated by 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and Enzyme-linked immunosorbent assay (ELISA), respectively. Use of ACEI/ARB (p=0.032), pathologic T stage (p<0.001), pathologic N stage (p=0.012), tumor stage (p=0.006), and tumor location (p=0.032) were significantly associated with superior overall survival. In multivariate comparison, use of ACEI/ARB (p=0.006), tumor stage (p=0.002), and tumor location (p=0.014) represented the independent prognosticators of superior overall survival. In cell lines, ACEIs/ARBs inhibit cell proliferation and VEGF secretion in a dose-dependent manner. ACEIs/ARBs administration is independently associated with superior overall survival in patients with esophageal squamous cell carcinoma receiving esophagectomy. Our data support further investigation of the role of RAS inhibitors as a potential therapy in esophageal squamous cell carcinoma.
Highlights
The aim of this study is to evaluate whether the administration of renin-angiotensin system (RAS) inhibitors, angiotensin-I converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), is associated with treatment outcome in patients with esophageal squamous cell carcinoma
Wilop et al reported that addition of an ACEI or ARB to platinum-base first line chemotherapy might contribute to prolonging survival in patients with advanced non-small-cell lung cancer.[18]
Two prospective studies showed that use of a ACEI or ARB was effective as a salvage therapy in the treatment of renal cell carcinoma and prostate cancer.[22,23]
Summary
The aim of this study is to evaluate whether the administration of renin-angiotensin system (RAS) inhibitors, angiotensin-I converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), is associated with treatment outcome in patients with esophageal squamous cell carcinoma. Conclusions: ACEIs/ARBs administration is independently associated with superior overall survival in patients with esophageal squamous cell carcinoma receiving esophagectomy. Previous studies showed that the angiotensin type 1 receptor is expressed in different malignancies, and has been reported to be significantly associated with tumor growth, metastasis, and angiogenesis.[5,6] The local RAS is known to promote angiogenesis and proliferation via vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR) expression,[7,8] and ACEI/ ARB suppress tumor progression by reduction of cancer proliferation and inhibition of neovascularization. Some studies reported that treatment with ACEI/ARB combined with or without chemotherapy might improve clinical outcome in patients with various type cancers, including pancreatic cancer, urothelial cancer, and gastric cancer.[9,10,11,12]
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