regarding the mechanism whereby pcyt2 influences cancer development, a previous report showed that pcyt2 downregulation - induced phosphoethanolamine ( petn ) accumulation correlated with tumor growth under nutrient starvation, thereby pcyt2 overexpression reduced petn levels and tumor growth [ 18 ]. however, in the present, we found that cdp - etn supplementation inhibited hcc migration, invasion and proliferation. in our previous study, we showed that the levels of bax and cleaved caspase - 3 were significantly increased whereas bcl - 2 was significantly reduced in the livers of type 2 diabetic mice and l02 cells after stimulation with high glucose and free fatty acids ( hg & ffa ) ( 12 ). cdp - etn ( 100 μm ) protected cells from hg & ffa - induced apoptosis by reducing bax and cleaved caspase - 3 levels as well as and increasing bcl - 2 levels [ 12 ]. whether pcyt2 downregulation induced petn accumulation contributes to hcc development further study. increasing evidence suggests that pcyt2 is aberrantly expressed in various models of liver disease and may predict clinical outcomes in patients. pcyt2 is instrumental in the deregulation of these processes leading to the development of obesity, insulin resistance, liver steatosis and dyslipid emia [ 28 ]. cdp - etn supplementation has been reported to alleviate pcyt2 deficiency engendering age - dependent and insulin - resistant non - alcoholic steatohepatitis to improve patient prognosis [ 20, 29 – 31 ]. chronic administration of peroxisome proliferators can increase the content of hepatic pc and pe for hepatomegaly and proliferation as well as cause liver cancer in rodents [ 32, 33 ]. based on the current studies, we hypothesized that pcyt2 may be involved in the regulation of cellular processes in hcc. therefore, we utilized in vivo and in vitro validation methods to assess the expression and mechanistic roles of pcyt2 in liver cancer cells. herein, pcyt2 overexpression was determined to inhibit hcc cell proliferation, migration and invasion both in vitro and in vivo. and, the number and morphology of mitochondria in hcc cells overexpressing pcyt2 were significantly different from those in hcc cells without any treatment, such as a decrease in the number of mitochondria and swelling of the mitochondria. these changes suggest that pcyt2 affects the mitochondrial function of cells. notably, when the hepg2 cells received cdp - etn supplementation, their proliferation, migration, and invasion were inhibited in vitro. notably, the atp level decreased in hcc cells following the overexpression of pcyt2, and the cells were found to be accompanied by mitochondrial damage using transmission electron microscopy. however, previous reports have indicated that pcyt2 is present only in the endoplasmic reticulum of hepatocytes [ 14, 34 ]. additionally, the phenotype of liver pcyt2 - / - knockout mice showed no signs of liver injury, however, they experienced massive accumulation of liver triglycerides ( tag ) [ 35 ]. therefore, we hypothesized that the influence of pcyt2 on mitochondrial function is mediated by metabolites such as tag, dag, and pe. however, further studies are needed to clarify whether the pcyt2 exerted inhibition of hcc cells alleviates mitochondrial damage. as understanding, the mechanism whereby pcyt2 overexpression causes mitochondrial damage will deepen our understanding of pcyt2 regulation in hcc cells. in conclusion, this study provided compelling data demonstrating the aberrant expression and functional role of pcyt2 in hepg2 cells. pcyt2 expression levels were lower in hepg2 than in l02. furthermore, pcyt2 overexpression in hepg2 cells induced mitochondrial damage; inhibited proliferation, invasion, and migration; and promoted cell apoptosis.