Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran; Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.
Department of Medical Biotechnology, Faculty of Medicine, Arak University of Medical Science, Arāk, Iran.
Int Immunopharmacol. 2020 Nov;88:106905. doi: 10.1016/j.intimp.2020.106905. Epub 2020 Sep 6.
Resveratrol is an anticancer phytochemical polyphenol isolated from a natural origin, without any significant side effects. Resveratrol was investigated in immunocompetent mice with regards to its possible effect on lung cancer metastasis. Cytotoxicity was assessed in three melanoma cell lines (B16F10, B6, and A375) by administration of 20 and 40 μM resveratrol. B16F10 cells were transfected with pT-tdTomato vector to express red fluorescent protein (RFP). RFP-B16F10 cells were injected IV into 3 groups of 20 C57BL/6 mice (ten for tests and others for survival). The three groups include PBS, no treatment, and resveratrol 40 mg/kg IP (4X/week for 3 weeks). Lung tissues were analyzed by TUNEL assay, Western blot, and immunohistochemistry. The in vitro growth of all melanoma cell lines was significantly suppressed by 40 μM resveratrol for 3 days. The mean survival rate of mice was enhanced and the lung tumor growth was inhibited by in vivo IP injection of 40 mg/kg resveratrol. Increased CXCL10 and IFN-γ levels and decreased angiogenesis and less tumor infiltration by Tregs were found in the lung tumors. In conclusion, lung metastasis of melanoma was effectively inhibited by resveratrol treatment.
白藜芦醇是一种从天然来源中分离出来的抗癌植物多酚，没有任何显著的副作用。本研究旨在探讨白藜芦醇对肺癌转移的可能作用。通过给予 20 和 40 μM 白藜芦醇，评估其对三种黑素瘤细胞系（B16F10、B6 和 A375）的细胞毒性。将 pT-tdTomato 载体转染 B16F10 细胞，以表达红色荧光蛋白（RFP）。将 RFP-B16F10 细胞静脉内注射到 20 只 C57BL/6 小鼠的三组中（十只为测试组，其余为生存组）。三组包括 PBS、无治疗和白藜芦醇 40mg/kg IP（每周 4 次，共 3 周）。通过 TUNEL 分析、Western blot 和免疫组织化学分析肺组织。40 μM 白藜芦醇处理 3 天可显著抑制所有黑素瘤细胞系的体外生长。体内 IP 注射 40mg/kg 白藜芦醇可提高小鼠的平均存活率并抑制肺肿瘤生长。在肺肿瘤中发现 CXCL10 和 IFN-γ 水平增加，血管生成减少，Tregs 浸润减少。总之，白藜芦醇治疗可有效抑制黑素瘤的肺转移。
