Background

According to the statistics of latest epidemic research, liver cancer poses a serous threat to human health with high incidence rate and mortality rate ranking sixth and fourth worldwide, respectively [1, 2]. An overwhelming majority of liver cancer cases were hepatocellular carcinoma (HCC), which has a high prevalence in multiple countries [3, 4]. The risk factors for HCC are complex and vary from area to area. While non-alcoholic fatty liver disease, hepatitis C virus infection and alcohol abuse were considered as the main risk elements for HCC in Japan and Western countries; the culprit behind HCC in eastern Asia and sub-Saharan Africa is hepatitis B virus (HBV) [5,6,7]. Although great achievements have been made for extending the life expectancy of HCC patients and a combination of therapies including surgical removal, radiotherapy, chemotherapy, radiofrequency ablation (RFA), and molecular targeted therapy have been applied for the treatment of HCC patients, most HCC patients were found to be in middle or later stage when diagnosed and the five-year survival rate of HCC patients remained at low level [8,9,10,11,24,25]. NC exerted significant suppressive effect on HCC xenograft tumor growth and caused notable decrease in tumor size of NC-treated group compared with control group [26,27,28,29,30,31,32,33,34]. Specifically, the contribution of angiogenesis, MAPK cascade and humoral immune response to the malignant process of HCC has been recorded in previous literature studies [35,36,37]. The serological testing and immunoblot assay by M Volkmann et al. revealed humoral immune response to p53 exclusively in HCC patients and the presence of p53 antibodies in HCC patients was not dependent on alpha-fetoprotein level [35]. The mitogen-activated protein kinase (MAPK) signaling pathways played essential roles in diverse biological events including survival, dissemination, and resistance to drug therapy of human tumor cells [38,39,40]. Wang et al. reported activation of MAPK signaling pathway during the promotion of HCC development stimulated by linc00601 upregulation [36]. HCC is rich in blood supply, and angiogenesis was indispensable for tumor growth, invasion and metastasis [41]. The work of Wang et al. disclosed that morphine could induce angiogenesis in HCC through activating PI3K/Akt/HIF-1α pathway and up-regulating VEGF expression [37]. Despite there have been no studies on the parts of ACP6 in activities of the above mentioned biological processes and pathways, the analysis results in this study provided potential presumptions of the molecular mechanism of ACP6 in HCC. Moreover, the in vitro experiments results in the present work supported the functional roles of ACP6 in proliferation and migration of HCC cells. The last high spot of this study was in vivo experiments on how NC affects the expression of ACP6 in HCC tissues. The pharmacologic mechanism of NC in tumor inhibition of HCC was far from been clarified and we conducted experiments on nude mice for further exploration. The significant suppression of NC on ACP6 in HCC tissues found in the present work might serve as a supplement to the explanations of pharmacologic actions of NC in fighting HCC.

Limitations of this paper were also existed. The protein expression of ACP6 in NC-treated xenograft and in Huh7 cells transfected with ACP6 siRNA should be examined by western blotting or immunohistochemistry. In vivo experiments are warranted in future work for validating the oncogenic roles of ACP6 in HCC and the molecular interactions between ACP6 and its co-expressed genes. The number of mice in the NC-treated was only two and control group was only three in the present study; both numbers of mice were too small for statistical analysis. The sufficient number of mice for subsequent statistical analysis should be eight to ten. More mice will be added in future in vivo experiments for guaranteeing the robustness of the in vivo experiment results.

Conclusions

In summary, we proved the overexpression of ACP6 in HCC and promotive effect of up-regulated ACP6 in the aggressive development of HCC. ACP6 was one of the potential targets of NC in HCC. The findings in the present study was anticipated to shed light on the molecular mechanism of HCC and lay a theoretical foundation for application prospect of ACP6 as a biomarker for HCC.