Lee Sol Hwa, Koo Bong Seong, Park Song Yi, Kim Young Min
Department of Biological Sciences and Biotechnology, College of Life Science and Nanotechnology, Hannam University, Yusung‑gu, Daejeon 305‑811, Republic of Korea.
Mol Med Rep. 2015 Aug;12(2):2777-83. doi: 10.3892/mmr.2015.3675. Epub 2015 Apr 24.
5-Fluorouracil (5-FU) has been used as a chemotherapeutic drug for various types of cancer, although the development of resistance remains a major limitation for its use in clinical settings. In the present study, the anti-angiogenic effects of resveratrol and 5-FU either alone or in combination were examined in a B16 murine melanoma model. Co-treatment using resveratrol and 5-FU inhibited cell proliferation more efficiently compared with use of either drug alone and the antiproliferative effect coincided with changes in the expression levels of AMP-activated protein kinase (AMPK), cyclooxygenase-2, vasodilator-stimulated phosphoprotein (VASP) and vascular endothelial growth factor (VEGF). Furthermore, co-treatment with resveratrol and 5-FU reduced tumor growth compared with that in the control group and this growth-inhibitory effect was associated with changes in the expression levels of AMPK, VASP and VEGF. Immunohistochemical staining for angiogenesis demonstrated that co-treatment with resveratrol and 5-FU reduced the number of microvascular vessels compared with that in the control group. These results suggested that co-treatment with resveratrol and 5-FU suppressed cell growth and angiogenesis in B16 murine melanoma tumors.
5-氟尿嘧啶（5-FU）已被用作治疗多种类型癌症的化疗药物，尽管耐药性的产生仍然是其在临床应用中的一个主要限制。在本研究中，在B16小鼠黑色素瘤模型中检测了白藜芦醇和5-FU单独或联合使用的抗血管生成作用。与单独使用任何一种药物相比，白藜芦醇和5-FU联合治疗更有效地抑制了细胞增殖，并且抗增殖作用与AMP激活蛋白激酶（AMPK）、环氧合酶-2、血管舒张刺激磷蛋白（VASP）和血管内皮生长因子（VEGF）表达水平的变化一致。此外，与对照组相比，白藜芦醇和5-FU联合治疗减少了肿瘤生长，并且这种生长抑制作用与AMPK、VASP和VEGF表达水平的变化有关。血管生成的免疫组织化学染色表明，与对照组相比，白藜芦醇和5-FU联合治疗减少了微血管数量。这些结果表明，白藜芦醇和5-FU联合治疗可抑制B16小鼠黑色素瘤肿瘤中的细胞生长和血管生成。
