Biomedical Research Institute, Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center, Shenzhen, 518036, China.
Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
Sci Rep. 2020 Oct 28;10(1):18515. doi: 10.1038/s41598-020-75598-1.
Several literature has shown that salinomycin (Sal) is able to kill various types of cancer cells through different signaling pathways. However, its effect on melanoma has seldom been reported. We examined the anti-cancer efficacy of Sal in melanoma cell lines, and found six of eight cell lines were sensitive to Sal. Given the fact that the roles of Sal are diverse in different cancer types, we were eager to figure out the mechanism involved in the current study. We noticed the most sensitive line, SK-Mel-19, showed a typical morphological change after Sal treatment. The autophagy inhibitor, 3-MA, could effectively suppress Sal-induced cell death. It could also facilitate the increase of autophagic markers and reduce the turnover of autophagosomes, which resulted in an aberrant autophagic flux. On the other hand, Sal could stimulate endoplasmic reticulum stress and cause an accumulation of dysfunctional mitochondria. We also discovered a potential correlation between LC3B mRNA level and its sensitivity to Sal in 43 clinical melanoma samples. Overall, our results indicated that Sal could have multiple effect on melanoma cells and induce autophagic cell death in certain kinds of cells, which provided a new insight into the chemotherapy for melanoma.
已有多项文献表明，盐霉素（Salinomycin）能够通过不同的信号通路杀死各种类型的癌细胞。然而，其对黑色素瘤的作用却鲜有报道。我们研究了盐霉素对黑色素瘤细胞系的抗癌功效，发现其中 8 种细胞系中有 6 种对盐霉素敏感。鉴于盐霉素在不同类型的癌症中的作用多种多样，我们渴望在本研究中弄清楚所涉及的机制。我们注意到最敏感的 SK-Mel-19 细胞在盐霉素处理后表现出典型的形态变化。自噬抑制剂 3-MA 可有效抑制盐霉素诱导的细胞死亡。它还可以促进自噬标记物的增加，并减少自噬体的周转率，从而导致异常的自噬通量。另一方面，盐霉素可以刺激内质网应激并导致功能失调的线粒体积累。我们还在 43 份临床黑色素瘤样本中发现 LC3B mRNA 水平与其对盐霉素敏感性之间存在潜在相关性。总的来说，我们的研究结果表明，盐霉素可能对黑色素瘤细胞有多种作用，并在某些类型的细胞中诱导自噬性细胞死亡，为黑色素瘤的化疗提供了新的思路。
