FGF21 promotes the growth and proliferation of melanoma cells through regulating intracellular fatty acid oxidation / 中华整形外科杂志

ABSTRACT

Objective@#To explore the role and underlying molecular mechanisms of fibroblast growth factor 21 (FGF21) in the development of melanoma.@*Methods@#Quantitative RT-PCR was applied to investigate the mRNA levels of FGF21 in cells. FGF21 overexpression plasmid was used to transfect FGF21 in melanoma cells, and shRNA technology was used to knock down FGF21 expression in melanoma cells. CCK8 assay and BrdU staining were used to detect the abilities of cell growth and proliferation. RT-qPCR was used to evaluate the expression levels of fat acids-oxidation-associated genes PGC1a, CD36, CPT1a, CPT1b and CPT2. Melanoma cells with or without FGF21 overexpression were subcutaneously injected into nude mice to observe the tumorigenic ability of the cells.@*Results@#The mRNA expression level of FGF21 was about 10 times higher than that of melanocytes (P<0.05). After the specific knockdown of FGF21 or overexpression of FGF21 in melanoma cells, cell proliferation levels were significantly reduced or increased (P<0.05). In vitro experiments showed that the overexpression of FGF21 significantly promoted the fatty acid oxidation in melanoma cells in terms of increased PGC1a, CD36, CPT1a, CPT1b and CPT2 gene expression. Further studies found that after the inhibition of intracellular fatty acid oxidation by small molecule Etomoxir, the cell proliferation ability of Etomoxir group was significantly lower than that of the control group by CCK8 assay and BrdU staining (P<0.05). Meanwhile, the tumor growth of the nude mice with FGF21-overexpressed melanoma cells was dramatically enhanced, and the tumor diameters were significantly increased.@*Conclusions@#FGF21 could promote the growth and proliferation of melanoma cells through regulating intracellular fatty acid oxidation, which accelerates the deterioration of melanoma.