Jiang Qun-Qun, Liu Wei-Bing
Department of Dermatology, 404 Hospital of People's Liberation Army, No.8 of Baoquan Street, Huancui District, Weihai 264200, Shandong Province, China.
Med Sci (Paris). 2018 Oct;34 Focus issue F1:33-38. doi: 10.1051/medsci/201834f106. Epub 2018 Nov 7.
Malignant melanoma, one of the most aggressive skin cancers, has a very high mortality rate. Currently, the number of drugs to treat melanoma is low. Although new immunotherapeutic approaches based on the use of antibodies against immune checkpoints have shown long term responses, it is urgent to develop novel anti-melanoma drugs with a high efficiency and a low toxicity in a large number of patients. Lycorine, a natural product, has been reported to exert antitumor effects on some cancers. However, the impact of lycorine on melanoma cells is still unknown. Using the CCK8 assay, we found that lycorine can suppress the proliferation of melanoma A375 cells in a dose-time-dependent manner. Moreover, a transwell assay showed that lycorine inhibited the migration and invasion of A375 cells significantly. Further, lycorine treatment could induce the apoptosis of the A375 cells. Biochemical analyses showed that the expression level of the anti-apoptosis Bcl-2 protein decreased, while the expression of the pro-apoptosis protein Bax and active caspase-3 increased after lycorine treatment. Finally, using western blot assay, we found that the antitumor effects of lycorine on A375 cells might be through the inactivation of the PI3K/Akt signaling pathway. Based on these observations, we suggest that lycorine may be an interesting candidate for further studies on its ability to represent a novel antitumor drug for human melanoma treatment in the future.
恶性黑色素瘤是最具侵袭性的皮肤癌之一，死亡率极高。目前，治疗黑色素瘤的药物数量较少。尽管基于使用抗免疫检查点抗体的新型免疫治疗方法已显示出长期疗效，但迫切需要开发大量高效低毒的新型抗黑色素瘤药物。天然产物石蒜碱已被报道对某些癌症具有抗肿瘤作用。然而，石蒜碱对黑色素瘤细胞的影响仍不清楚。通过CCK8检测，我们发现石蒜碱能以剂量和时间依赖性方式抑制黑色素瘤A375细胞的增殖。此外，Transwell检测表明石蒜碱显著抑制A375细胞的迁移和侵袭。此外，石蒜碱处理可诱导A375细胞凋亡。生化分析表明，石蒜碱处理后，抗凋亡蛋白Bcl-2的表达水平降低，而促凋亡蛋白Bax和活性caspase-3的表达增加。最后，通过蛋白质免疫印迹法检测，我们发现石蒜碱对A375细胞的抗肿瘤作用可能是通过PI3K/Akt信号通路的失活实现的。基于这些观察结果，我们认为石蒜碱可能是未来进一步研究其作为人类黑色素瘤治疗新型抗肿瘤药物潜力的一个有趣候选物。
