Yang Hao, Liu Chang, Zhang Ya-Qi, Ge Ling-Tian, Chen Jun, Jia Xiao-Qin, Gu Rui-Xia, Sun Yun, Sun Wei-Dong
Medical and Pharmaceutical Institute, Yangzhou University, 11 Huaihai Road, Yangzhou City, Jiangsu Province 225001, PR China.
Jiangsu Key Laboratories of Dairy Biological Technology and Safety Control, Yangzhou University, Yangzhou 225127, Jiangsu Province, PR China.
Int Immunopharmacol. 2015 Feb;24(2):423-431. doi: 10.1016/j.intimp.2014.12.040. Epub 2015 Jan 13.
The present study aimed to investigate the anti-tumor activity of Ilexgenin A in B16-F10 murine melanoma and to evaluate its effect on the production of tumor-associated inflammatory cytokines. In vitro, our study showed that Ilexgenin A inhibited the proliferation of B16-F10 murine melanoma cells in a dose- and time-dependent manner, and this effect could be ascribed to the arrest of the cell cycle at G0/G1. In vivo, we evaluated the anti-tumor activity of Ilexgenin A in a tumor-bearing mouse model. The results showed that Ilexgenin A reduced the tumor weight by 51.13% (p<0.01). The Ilexgenin A treatment groups showed no apparent side effects during the treatment period. In addition, a histological analysis revealed that Ilexgenin A changed the cell morphology, and induced large areas of necrosis that correlated with a reduction in tumor size. The detection of inflammatory cytokines indicated that the IL-6 level decreased (p<0.001) and the TNF-α level increased (p<0.01) in mice treated with Ilexgenin A. Ilexgenin A also inhibited the IL-6 production of macrophages stimulated by melanoma conditioned medium (MCM) significantly (p<0.001). Importantly, Ilexgenin A dramatically prolonged survival time (p<0.001). In conclusion, Ilexgenin A could be regarded as a promising agent for the treatment of melanoma; it exerts anti-melanoma activity by arresting the cell cycle at G0/G1 and regulating IL-6 and TNF-α production.
本研究旨在探讨冬青素A对B16-F10小鼠黑色素瘤的抗肿瘤活性，并评估其对肿瘤相关炎性细胞因子产生的影响。在体外，我们的研究表明，冬青素A以剂量和时间依赖性方式抑制B16-F10小鼠黑色素瘤细胞的增殖，这种作用可能归因于细胞周期在G0/G1期的阻滞。在体内，我们在荷瘤小鼠模型中评估了冬青素A的抗肿瘤活性。结果表明，冬青素A使肿瘤重量降低了51.13%（p<0.01）。冬青素A治疗组在治疗期间未显示明显的副作用。此外，组织学分析显示，冬青素A改变了细胞形态，并诱导大面积坏死，这与肿瘤大小的减小相关。炎性细胞因子的检测表明，用冬青素A治疗的小鼠中IL-6水平降低（p<0.001），TNF-α水平升高（p<0.01）。冬青素A还显著抑制了黑色素瘤条件培养基（MCM）刺激的巨噬细胞的IL-6产生（p<0.001）。重要的是，冬青素A显著延长了生存时间（p<0.001）。总之，冬青素A可被视为一种有前途的黑色素瘤治疗药物；它通过将细胞周期阻滞在G0/G1期并调节IL-6和TNF-α的产生来发挥抗黑色素瘤活性。
