Sobolev Vladimir, Tchepourina Ekaterina, Soboleva Anna, Denisova Elena, Korsunskaya Irina, Mezentsev Alexandre
Laboratory of Physicochemical and Genetic Problems in Dermatology, Center for Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, Moscow 109029, Russia.
Moscow Center of Dermatovenerology and Cosmetology, Moscow 119071, Russia.
Cells. 2025 Apr 2;14(7):534. doi: 10.3390/cells14070534.
Changes in skin pigmentation, like hyperpigmentation or moles, can affect appearance and social life. Unlike locally containable moles, malignant melanomas are aggressive and can spread rapidly, disproportionately affecting younger individuals with a high potential for metastasis. Research has shown that the peroxisome proliferator-activated receptor gamma (PPAR-γ) and its ligands exhibit protective effects against melanoma. As a transcription factor, PPAR-γ is crucial in functions like fatty acid storage and glucose metabolism. Activation of PPAR-γ promotes lipid uptake and enhances sensitivity to insulin. In many cases, it also inhibits the growth of cancer cell lines, like breast, gastric, lung, and prostate cancer. In melanoma, PPAR-γ regulates cell proliferation, differentiation, apoptosis, and survival. During tumorigenesis, it controls metabolic changes and the immunogenicity of stromal cells. PPAR-γ agonists can target hypoxia-induced angiogenesis in tumor therapy, but their effects on tumors can be suppressive or promotional, depending on the tumor environment. Published data show that PPAR-γ-targeting agents can be effective in specific groups of patients, but further studies are needed to understand lesser-known biological effects of PPAR-γ and address the existing safety concerns. This review provides a summary of the current understanding of PPAR-γ and its involvement in melanoma.
皮肤色素沉着的变化，如色素沉着过度或痣，会影响外观和社交生活。与局部可控的痣不同，恶性黑色素瘤具有侵袭性，可迅速扩散，对具有高转移潜力的年轻个体影响尤为严重。研究表明，过氧化物酶体增殖物激活受体γ（PPAR-γ）及其配体对黑色素瘤具有保护作用。作为一种转录因子，PPAR-γ在脂肪酸储存和葡萄糖代谢等功能中起关键作用。PPAR-γ的激活促进脂质摄取并增强对胰岛素的敏感性。在许多情况下，它还能抑制乳腺癌、胃癌、肺癌和前列腺癌等癌细胞系的生长。在黑色素瘤中，PPAR-γ调节细胞增殖、分化、凋亡和存活。在肿瘤发生过程中，它控制代谢变化和基质细胞的免疫原性。PPAR-γ激动剂可在肿瘤治疗中靶向缺氧诱导的血管生成，但其对肿瘤的影响可能是抑制性的或促进性的，这取决于肿瘤环境。已发表的数据表明，靶向PPAR-γ的药物在特定患者群体中可能有效，但需要进一步研究以了解PPAR-γ鲜为人知的生物学效应并解决现有的安全问题。本综述总结了目前对PPAR-γ及其在黑色素瘤中的作用的理解。
