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Targeting of the COX-2/PGE2 axis enhances the antitumor activity of T7 peptide in vitro and in vivo.

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机构: [1]Department of Hepatobiliary, Pancreas and Spleen Surgery, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning,China [2]Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and ShandongAcademy of Medical Sciences, Jinan, China [3]Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China [4]School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, China [5]Department of GeneralSurgery, Shandong Provincial Qianfoshan Hospital, The First Affiliated Hospital of Shandong First Medical University, Jinan, China
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关键词: Tumstatin T7 peptide integrin cyclooxygenase-2 hypoxia

摘要:
T7 peptide is considered as an antiangiogenic polypeptide. The presents study aimed to further detect the antiangiogenic mechanisms of T7 peptide and determine whether combining T7 peptide and meloxicam (COX-2/PGE2 specific inhibitor) could offer a better therapy to combat hepatocellular carcinoma (HCC). T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3β1 and αvβ3 pathways. Cell proliferation, migration, apoptosis, or tube formation ability were detected, and the expression of integrin-associated regulatory proteins was detected. The anti-tumor activity of T7 peptide, meloxicam, and their combination were evaluated in HCC tumor models established in mice. T7 peptide suppressed the proliferation, migration, tube formation, and promoted the apoptosis of endothelial cells under both normoxic and hypoxic conditions via integrin α3β1 and αvβ3 pathways. Meloxicam enhanced the activity of T7 peptide under hypoxic condition. T7 peptide partly inhibited COX-2 expression via integrin α3β1 not αvβ3-dependent pathways under hypoxic condition. T7 peptide regulated apoptosis associated protein through MAPK-dependent and -independent pathways under hypoxic condition. The MAPK pathway was activated by the COX-2/PGE2 axis under hypoxic condition. The combination of T7 and meloxicam showed a stronger anti-tumor effect against HCC tumors in mice. The data highlight that meloxicam enhanced the antiangiogenic activity of T7 peptide in vitro and in vivo.

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出版当年[2020]版:
大类 | 2 区 医学
小类 | 2 区 药学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 药学
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出版当年[2019]版:
Q1 PHARMACOLOGY & PHARMACY
最新[2023]版:
Q1 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [1]Department of Hepatobiliary, Pancreas and Spleen Surgery, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning,China
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通讯机构: [1]Department of Hepatobiliary, Pancreas and Spleen Surgery, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning,China [*1]Department of Hepatobiliary, Pancreas and Spleen Surgery, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
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