All-trans retinoic acid suppresses the angiopoietin-Tie2 pathway and inhibits angiogenesis and metastasis in esophageal squamous cell carcinoma
Authors: Luqian Sang
Daoming Li
Jingyao Lian
Shanshan Li
Jane J Yu
Yanjuan Lu
Taiying Lu
Xiangyu Zheng
Na Li
Huijuan Cui
Linda Zhang
Ying Wang
Journal: PloS one (2017)
Discipline: Multidisciplinary
Keywords: Esophageal squamous cell carcinoma; All-trans retinoic acid; Angiopoietin; Tie-2; EC1 cells
Affiliations: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China., Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China., School of Life Sciences, Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China., Department of Oncology, Zhengzhou First People's Hospital, Zhengzhou, Henan Province, People's Republic of China., Department of Oncology, The Chinese People's Liberation Army 150 Central Hospital, Luoyang, Henan Province, People's Republic of China., Department of Behavioral Neuroscience, Northeastern University, Boston, MA, United States of America., Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America.

Abstract:  Esophageal squamous cell carcinoma (ESCC) is the second common cancer in Henan province and is well-known for aggressiveness and dismal prognosis. Adjuvant therapies, chemotherapy, radiotherapy and endoscopic treatment have not improved survival rates in patients with late stage esophageal carcinoma. All-trans retinoic acid (ATRA) is the active ingredient of Vitamin A and affects a wide spectrum of biological processes including development, growth, neural function, immune function, reproduction, and vision. It is one of the most potent therapeutic agents used for treating cancers, especially lung adenocarcinomas. ATRA inhibits metastatic potential and angiogenesis in several tumor models. We investigated the effects of ATRA on the expression of angiopoietin 1 (Ang-1), angiopoietin 2 (Ang-2) and receptor Tie-2 in EC1 cells in vitro. We also assessed the growth and migration of EC1 cells in vitro. ATRA treatment caused 29.5% and 40.3% reduction of the growth of EC1 cells after 24 hours and 48 hours, relative to the control. ATRA plus fluorouracil treatment reduced the viability more strongly than either drug alone, indicating an additive effect. Moreover, ATRA decreased EC1 migration by 87%. Furthermore, ATRA treatment led to a marked decrease of the transcript levels of Ang-1, Ang-2, Tie-2, VEGF, and VEGF receptors, as assessed by real-time RT-PCR. Importantly, the protein levels of Ang-1, Ang-2 and Tie-2 were reduced by ATRA treatment. In vivo, we found ATRA treatment suppressed the tumor growth and improved the cachexia of mice. Importantly, ATRA treatment decreased the expression of CD31, Ang-1, Ang-2 and Tie-2 in subcutaneous tumors of EC1 cells. Collectively, our findings demonstrate that ATRA exhibits a dose- and temporal-dependent effect on the metastatic behavior, suppresses the angiopoietin-Tie2 pathway and inhibits angiogenesis and the progression of xenograft tumors of EC1 cells. 

Retracted: No

PubPeer comments:
 Authors should review Figure 1E. Clearly someone was disappointed with the actual results. *** Inverse ![file] *** Full figure ![file] ,