He Liwei, Fan Fangtian, Hou Xianbang, Gao Cuixiang, Meng Li, Meng Shu, Huang Shiwen, Wu Hongyan
Department of Pharmacology, Nanjing University of Chinese Medicine Hanlin College, Taizhou, China; Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Pharmacology, Nanjing University of Chinese Medicine Hanlin College, Taizhou, China.
J Surg Res. 2017 Sep;217:113-122. doi: 10.1016/j.jss.2017.05.009. Epub 2017 May 10.
To explore the impact of Resveratrol (RSV) on the angiogenic potential of activated platelets and to elucidate the underlying mechanism.
Vascular endothelial growth factor concentrations were measured by enzyme-linked immunosorbent assay. Capillary tube formation assay was used to examine the impact of RSV on the angiogenic potential of activated platelets. The levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate (cGMP) in the supernatant were evaluated using corresponding enzyme-linked immunosorbent assay kits. Immunoblotting assays were used to determine the expression of vasodilator-stimulated phosphoprotein and Akt phosphorylation. A pulmonary metastasis experiment with male nude mice model was performed to test the effect of RSV on pulmonary metastasis and angiogenesis in vivo.
RSV inhibited platelets-mediated angiogenic responses induced by adenosine diphosphate (ADP)ADP through increased cGMP generation and cGMP-mediated vasodilator-stimulated phosphoprotein phosphorylation along with reduced intracellular Ca mobilization. In addition, RSV attenuated the platelet secretion and angiogenic responses induced by A549 cells in vitro and suppressed A549 lung cancer metastasis and angiogenesis in nude mice.
RSV is a potential therapeutic drug for the prevention of tumor metastasis by interrupting the platelet-tumor cell amplification loop.
探讨白藜芦醇（RSV）对活化血小板血管生成潜能的影响并阐明其潜在机制。
采用酶联免疫吸附测定法检测血管内皮生长因子浓度。使用毛细管形成试验检测RSV对活化血小板血管生成潜能的影响。使用相应的酶联免疫吸附测定试剂盒评估上清液中环磷酸腺苷和环磷酸鸟苷（cGMP）的水平。采用免疫印迹法测定血管舒张刺激磷蛋白的表达和Akt磷酸化。利用雄性裸鼠模型进行肺转移实验，以测试RSV对体内肺转移和血管生成的影响。
RSV通过增加cGMP生成、cGMP介导的血管舒张刺激磷蛋白磷酸化以及减少细胞内钙动员，抑制二磷酸腺苷（ADP）诱导的血小板介导的血管生成反应。此外，RSV减弱了体外A549细胞诱导的血小板分泌和血管生成反应，并抑制了裸鼠体内A549肺癌转移和血管生成。
RSV是一种潜在的治疗药物，可通过中断血小板 - 肿瘤细胞扩增环来预防肿瘤转移。
