Melanoma incidence increases every year worldwide and is responsible for 80% of skin cancer deaths. Due to its metastatic potential and resistance to almost any treatments such as chemo, radio, immune and targeted-therapy, the patients still have a poor prognosis, especially at metastatic stage. Considering that, it is crucial to find new therapeutic approaches to overcome melanoma resistance. Here we investigated the effect of cisplatin (CDDP), one of the chemotherapeutic agents used for melanoma treatment, in association with nutritional deprivation in murine melanoma cell lines. Cell death and autophagy were evaluated after the treatment with cisplatin, nutritional deprivation and its association using an in vitro model of murine melanocytes malignant transformation to metastatic melanoma. Our results showed that nutritional deprivation augmented cell death induced by cisplatin in melanoma cells, especially at the metastatic subtype, with slight effects on melanocytes. Mechanistic studies revealed that although autophagy was present at high levels in basal conditions in melanoma cells, was not essential for cell death process that involved mitochondrial damage, reactive oxygen species production and possible glycolysis inhibition. In conclusion, nutritional shortage in combination with chemotherapeutic drugs as cisplatin can be a valuable new therapeutic strategy to overcome melanoma resistance.

黑色素瘤的发病率在全球范围内逐年增加，并导致80％的皮肤癌死亡。由于它具有转移潜力，并且对化学疗法，放射疗法，免疫疗法和靶向疗法等几乎所有治疗方法都没有抵抗力，因此患者的预后仍然很差，尤其是在转移阶段。考虑到这一点，找到克服黑素瘤耐药性的新治疗方法至关重要。在这里，我们研究了顺铂（CDDP）（一种用于黑色素瘤治疗的化学治疗剂）与小鼠黑色素瘤细胞系营养剥夺相关的作用。在体外用顺铂治疗，营养剥夺及其相关性后，评估细胞死亡和自噬鼠黑色素细胞恶性转化为转移性黑色素瘤的模型。我们的结果表明，营养剥夺增加了顺铂在黑素瘤细胞中引起的细胞死亡，尤其是在转移性亚型中，对黑素细胞的影响很小。机理研究表明，尽管黑素瘤细胞在基础条件下自噬水平很高，但对于涉及线粒体损伤，活性氧产生和可能的糖酵解抑制的细胞死亡过程而言，并不是必需的。总之，营养不足与化疗药物（如顺铂）相结合可能是克服黑素瘤耐药性的一种有价值的新治疗策略。