Department of Hepatobiliary, Pancreas and Spleen Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Drug Deliv. 2021 Dec;28(1):844-855. doi: 10.1080/10717544.2021.1914776.
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 and .
T7 肽被认为是一种抗血管生成多肽。本研究旨在进一步检测 T7 肽的抗血管生成机制，并确定 T7 肽与美洛昔康（COX-2/PGE2 特异性抑制剂）联合应用是否能为治疗肝细胞癌（HCC）提供更好的治疗方法。T7 肽通过整合素 α3β1 和 αvβ3 途径，在常氧和低氧条件下均抑制内皮细胞的增殖、迁移、管形成，并促进其凋亡。检测细胞增殖、迁移、凋亡或管形成能力，并检测整合素相关调节蛋白的表达。在小鼠建立的 HCC 肿瘤模型中评估了 T7 肽、美洛昔康及其组合的抗肿瘤活性。T7 肽通过整合素 α3β1 和 αvβ3 途径，在常氧和低氧条件下均抑制内皮细胞的增殖、迁移、管形成，并促进其凋亡。美洛昔康增强了 T7 肽在低氧条件下的活性。T7 肽通过整合素 α3β1 而非 αvβ3 依赖性途径部分抑制 COX-2 的表达在低氧条件下。T7 肽通过 MAPK 依赖性和非依赖性途径调节凋亡相关蛋白在低氧条件下。MAPK 通路在低氧条件下被 COX-2/PGE2 轴激活。T7 与美洛昔康联合应用对小鼠 HCC 肿瘤表现出更强的抗肿瘤作用。这些数据表明，美洛昔康增强了 T7 肽的抗血管生成活性，并且 。
