Lentivirus­mediated MDA7/IL24 expression inhibits the proliferation of hepatocellular carcinoma cells.

MDA7/IL24 is a member of the IL­10 gene family that functions as a cytokine. Notably, supra­physiological endogenous MDA7 levels have been indicated to suppress tumor growth and induce apoptosis in different cancer types. In the present study, MDA7 roles were investigated during the proliferation of hepatocellular carcinoma (HCC) cells and the molecular mechanisms underlying this process. A lentiviral vector expressing MDA7/IL24 (LV­MDA7/IL24) was constructed and used to infect HCC SMMC­7721 cells. The expression levels of MDA7/IL24 in these cells were determined using RT­qPCR and western blot analysis. The effects of LV­MDA7/IL24 on cell proliferation were analyzed using MTT and colony formation assays. Furthermore, the influence of LV­MDA7/IL24 on cell apoptosis and cell cycle distribution were detected using flow cytometry. The underlying molecular mechanisms were investigated using microarray and western blot analysis. The expression of MDA7/IL24 was confirmed to be significantly increased in the cells infected with LV­MDA7/IL24 compared with that the negative­control infected group. Lentivirus­mediated MDA7/IL24 expression was found to inhibit HCC cell proliferation and colony formation, and it also induced cell arrest and apoptosis. Microarray analysis and western blotting results indicated that multiple cancer­associated pathways and oncogenes are regulated by MDA7/IL24, including cell cycle regulatory and apoptosis activation pathway. In conclusion, it was determined that MDA7/IL24 inhibits the proliferation and reduces the tumorigenicity of HCC cells by regulating cell cycle progression and inducing apoptosis, indicating that it may be used as a potential prognostic and therapeutic target in HCC.

Prognostic value of serum AFP, AFP-L3, and GP73 in monitoring short-term treatment response and recurrence of hepatocellular carcinoma after radiofrequency ablation.

PURPOSE: Alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and Golgi protein 73 (GP73) levels have been widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to investigate whether these tumor markers could be used to monitor short-term treatment response and recurrence of HCC in patients undergoing radiofrequency ablation (RFA). METHODS: Between July 2012 and July 2013, 53 consecutive patients with newly diagnosed HCC were prospectively enrolled in this study. Among these, 32 patients underwent RFA, after which they were followed up prospectively at the First Hospital of Jilin University in China. RESULTS: AFP, AFP-L3, and GP-73 values pre-RFA were not associated with tumor size, whereas AFP and GP-73 levels tended to be associated with tumor number, the presence of vascular invasion, deterioration of liver function, advanced-stage disease, and a poor performance status. GP-73 levels were dramatically elevated in the patients with hepatitis C-associated HCC. Neither pre-RFA nor 1-month post-RFA tumor marker values were associated with short-term outcome. The short-term recurrence rate of AFP-positive patients measured 1 month post-RFA was obviously higher than that of AFP-negative patients. CONCLUSIONS: AFP and GP-73 values were associated with clinical variables representing tumor growth and invasiveness, and the AFP value measured 1 month post-RFA was a strong predictor of short-term recurrence in patients with HCC.