3‐O‐Acetyloleanolic acid inhibits angiopoietin‐1‐induced angiogenesis and lymphangiogenesis via suppression of angiopoietin‐1/Tie‐2 signaling

Tumor angiogenesis and lymphangiogenesis are important processes in tumor progression and metastasis. The inhibitory effects of 3‐O‐acetyloleanolic acid (3AOA), a pentacyclic triterpenoid compound isolated from Vigna sinensis K., on tumor‐induced angiogenesis and lymphangiogenesis in vitro and in vivo were studied. Angiopoietin‐1 is an important angiogenic and lymphangiogenic factor secreted from colon carcinoma CT‐26 cells under hypoxia conditions. 3AOA inhibited proliferation, migration, and tube formation of angiopoietin‐1‐treated human umbilical vein endothelial cells (HUVEC) and human lymphatic microvascular endothelial cells (HLMEC). 3AOA reduced angiogenesis and lymphangiogenesis in angiopoietin‐1‐stimulated Matrigel plugs. Also, 3AOA inhibited tumor growth and tumor‐induced angiogenesis and lymphangiogenesis in an angiopoietin‐1‐induced CT‐26 allograft colon carcinoma animal model. 3AOA inhibited activation of the angiopoietin‐1 receptor Tie‐2 and activation of the downstream signaling factors FAK, AKT, and ERK1/2 that are involved in the angiopoietin‐1/Tie‐2‐signaling pathway. Thus, 3AOA has an inhibitory effect on angiogenesis and lymphangiogenesis induced by angiopoietin‐1 both in vitro and in vivo, and the inhibitory effect of 3AOA is probably due to suppression of angiopoietin‐1/Tie‐2 signaling in HUVEC and HLMEC.     

miR-377-5p通过下调VEGF-C对结肠癌的血管和淋巴管生成的影响研究

目的探讨miR-377-5p通过下调VEGF-C对结肠癌的血管和淋巴管生成的影响研究。方法该实验分为3组,miR-377-5p干扰组、miR-377-5p阴性对照组和miR-377-5p过表达组。采用实时荧光RT-PCR、Western blot、CCK-8、流式细胞、细胞划痕、Transwell、血管生成实验检测miR-377-5p m RNA和蛋白表达、细胞增殖、凋亡、迁移、侵袭、血管和淋巴管生成。结果与正常结肠组织对比,结肠癌组织中miR-377-5p m RNA和miR-377-5p蛋白的表达明显低于正常结肠组织(均P<0.05);与miR-377-5p干扰组相比,miR-377-5p阴性对照组和miR-377-5p过表达组中的m RNA及蛋白显著升高(均P<0.05),与miR-377-5p阴性对照组相比,miR-377-5p过表达组的m RNA及蛋白明显增加(P<0.05);与miR-377-5p干扰组相比,miR-377-5p阴性对照组和miR-377-5p过表达组的结肠癌细胞增殖能力明显降低(P<0.05),与miR-377-5p阴性对照组相比,miR-377-5p过表达组的结肠癌细胞增殖能力显著降低(P<0.05);与miR-377-5p干扰组相比,miR-377-5p阴性对照组和miR-377-5p过表达组的结肠癌细胞增殖凋亡明显升高(P<0.05),与miR-377-5p阴性对照组相比,miR-377-5p过表达组的结肠癌细胞凋亡能力显著升高(P<0.05);伤口愈合实验显示,miR-377-5p过表达组的结肠癌细胞的迁移能力显著低于miR-377-5p干扰组和miR-377-5p阴性对照组(P<0.05);miR-377-5p过表达组的结肠癌细胞的侵袭能力也明显低于miR-377-5p干扰组和miR-377-5p阴性对照组(P <0.05);miR-377-5p过表达组的VEGF-A、VEGF-C和P-Akt、VEGFR-3蛋白水平显著低于miR-377-5p干扰组和miR-377-5p阴性对照组(P<0.05);miR-377-5p过表达组的MVD(微血管密度)和LMVD(淋巴微血管密度)显著低于miR-377-5p干扰组和miR-377-5p阴性对照组(P<0.05)。结论 miR-377-5p在结肠癌中低表达,抑制了结肠癌细胞的增殖、细胞迁移和侵袭,促进了结肠癌细胞的凋亡能力,并直接靶向VEGF-C抑制肿瘤的血管和淋巴管生成。     

食管癌淋巴管生成研究进展

食管癌预后差,易早期出现淋巴结转移。肿瘤发生淋巴结转移与肿瘤的淋巴管生成及淋巴管生成因子的表达有关。肿瘤进展过程与淋巴管生成有关。近年来,关于食管癌淋巴管生成及淋巴结转移的研究逐渐成为食管癌相关研究的热点。现将食管癌淋巴管生成方面的研究进展综述如下。     

CCBE1在舌鳞癌癌旁组织中的表达与癌周淋巴管增生及患者预后的相关性

目的 探究CCBE1在舌鳞癌癌旁组织中的表达与癌周淋巴管增生、颈淋巴结转移及患者预后间是否存在相关性。方法 对44例cT1-2N0舌鳞癌癌旁组织病理切片标本进行淋巴管密度定量分析,采用D2-40作为淋巴管内皮标记物标定淋巴管并进行计数。将淋巴管密度低的22例纳入A组,淋巴管密度相对高的22例纳入B组。同时对两组标本中胶质和钙结合表皮生长因子域 1（CCBE1）的表达情况通过免疫组化、免疫荧光和Western blot进行测定。免疫组化检测90例舌鳞状细胞癌病理标本中CCBE1的表达情况,并完善相关随访资料,进行统计分析。结果 免疫组化及Western blot结果显示A组中CCBE1的高表达率明显低于B组,差异有统计学意义（P<0.05）。免疫荧光实验显示CCBE1与D2-40存在“共定位”现象。90例舌鳞癌患者中发生颈淋巴结转移者CCBE1的高表达率较之无淋巴结转移者明显更高（P<0.05）,死亡组CCBE1的高表达率也明显高于存活组（P<0.05）。结论 CCBE1在舌鳞癌组织中的表达量与癌周淋巴管增生、颈淋巴结转移及患者的5年生存率有关,可作为判断舌鳞癌患者预后的独立预测因子。     

AIBP: A Novel Molecule at the Interface of Cholesterol Transport,Angiogenesis, and Atherosclerosis

Cardiovascular disease, which is often driven by hypercholesterolemia and subsequent coronary atherosclerosis, is the number-one cause of morbidity and mortality in the United States. Based on long-term epidemiological studies, high-density lipoprotein cholesterol (HDL-C) levels are inversely correlated with risk for coronary artery disease (CAD). HDL-mediated reverse cholesterol transport (RCT) is responsible for cholesterol removal from the peripheral tissues and return to the liver for final elimination.1 In atherosclerosis, intraplaque angiogenesis promotes plaque growth and increases plaque vulnerability. Conceivably, the acceleration of RCT and disruption of intraplaque angiogenesis would inhibit atherosclerosis and reduce CAD. We have identified a protein called apoA-I binding protein (AIBP) that augments HDL functionality by accelerating cholesterol efflux. Furthermore, AIBP inhibits vascular endothelial growth factor receptor 2 activation in endothelial cells and limits angiogenesis.2 The following discusses the prospect of using AIBP as a novel therapeutic approach for the treatment of CAD.