Abstract:

Objective To discuss the effect of apolipoprotein C1 （APOC1） expression on the proliferation and apoptosis of the hepatocellular carcinoma cells， and to preliminarily clarify the related molecular mechanism. Methods The expression level of APOC1 mRNA in hepatocellular carcinoma tissue and its relationship with the prognosis of the patient were analyzed by The Cancer Genome Atlas （TCGA） Database； real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of APOC1 mRNA in different hepatocellular carcinoma cells； the human liver cancer HepG2 cells with low APOC1 expression were selected as the subjects. The HepG2 cells were transfected with pcDNA3.1-APOC1 plasmid to over-express APOC1 （APOC1 over-expression group），and the HepG2 cells transfected with empty vector pcDNA3.1 were regarded as control group. MTS assay and 5-ethynyl-2'-deoxyuridine （EdU） staining were used to detect the proliferative activities and proliferation rates of the cells in two groups； Transwell chamber assay was used to detect the numbers of migration cells in two groups；flow cytometry and TUNEL assay were used to detect the percentages of the cells at different cell cycles and apoptotic rates in two groups；Western blotting method was used to detect the expression levels of extracellular regulated protein kinase （ERK）， phosphorylated ERK （p-ERK）， protein kinase B （AKT）， phosphorylated AKT （p-AKT）， B-cell lymphoma-2 （Bcl-2）， and cleaved cysteinyl aspartate specific proteinase-3（cleaved caspase-3） proteins in the cells in two groups. Results The TCGA Database results showed that the expression level of APOC1 mRNA in hepatocellular carcinoma tissue was lower than that in normal liver tissue （P<0.05）， and the patients with low expression of APOC1 mRNA had poor prognosis. The RT-qPCR results showed that the expression level of APOC1 mRNA in the HepG2 cells was the lowest， and the HepG2 cells were chosen for the subsequent research. Compared with control group， the proliferative activity and proliferation rate of the cells in APOC1 over-expression group were decreased （P<0.05 or P<0.01），the number of migration cells was decreased （P<0.01），and the percentage of the cells at S phase and the apoptotic rate were significantly increased （P<0.01）. Compared with control group， the expression levels of p-ERK， p-AKT， and Bcl-2 proteins in the cells in APOC1 over-expression group were significantly decreased （P<0.05），and the expression level of cleaved caspase-3 protein was increased （P<0.01）. Conclusion High expression of APOC1 can inhibit the proliferation of the human liver cancer HepG2 cells and induce the apoptosis，and its mechanism may be related to inhibition of the expressions of p-ERK，p-AKT，Bcl-2 proteins and promotion of the expression of cleaved caspase-3 protein.

Key words: Apolipoprotein C1, Liver neoplasm, Cell proliferation, Apoptosis, Human liver cancer HepG2 cell