Study On Anti-hepatoma Effects And Mechanism Of Lycopene Nanodispersion

Objective: To prepare lycopene nanodispersion and evaluate the anti-hepatoma effect of lycopene nanodispersion in vitro and in vivo and its mechanism.Methods: Lycopene nanodispersion was prepared by the emulsification-evaporation process. Scavenging effects of lycopene nanodispersion on reactive oxygen species (·OH and H2O2) were investigated by spectrophotometric methods in vitro. Mice transplanted with H22 liver tumor were established and antitumor effect of lycopene naonodispersion in vivo was analyzed. Study of antioxidant activity, pathological technology and immunohistochemical technology were utilized to detect the antitumor mechanism in vivo. The MTT assay was used to examine the proliferation arrest of carcinoma cell line (HepG2) and normal cell line (L-02) in vitro. And cell morphological observation, biochemical test and immunohistochemical technology were used to detect the antitumor mechanism in vitro.Results: Lycopene nanodispersion was obtained and the particle size was 261nm. The dispersive property was effectively improved. Lycopene nanodispersion had strong scavenging effects in both radical systems and the anti-radical activities. At the same concentration, the scavenging capabilities of lycopene nanodispersion were stronger than the lycopene dissolved in THF. Mice transplanted with H22 liver tumor were treated with 1.95 mg·kg-1and 3.9 mg·kg-1 lycopene nanodispersion for 10 days respectively, the tumor growth inhibition rate were 32.37% and 54.34%, which were higher than the inhibiton rate caused by 3.9 mg·kg-1 unprocessed lycopene. Lycopene nanodispersion could significantly increase the activities of GSH-Px, and decrese the content of MDA of blood serum of mice. It also could significantly increase the activities of T-AOC and SOD activity, and the reduction of the content of MDA and H2O2 of liver of mice. The results of pathological technology demonstrated that inflammatory cells infiltrated in the surrounding connective tissue of tumors. Lycopene nanodispersion could down-regulate the expression of proliferating cell nuclear antigen (PCNA) in Hepatocarcinoma H22. The MTT assay showed that lycopene nanodispersion had the selective toxicity on HepG2 cells. Tween-20, as emulsifier for lycopene nanodispersion, also had the same selective toxicity. The activities of LDH in HepG2 cells culture supernatant significantly increased after 24h exposure to lycopene nanodispersion and emulsifier, which indicated that they may induce some damages on HepG2 cells membrane. Lycopene nanodispersion could down-regulate the expression of PCNA in HepG2 cells and tween-20 didn't have the same effect.Conclusion: Lycopene nanodispersion was able to inhibit potently the gowth of hepatoma in vitro and in vivo. The mechanism may be associated with increase of anti-oxidation activity, down regulation PCNA expression and direct cytotoxicity.