Natural Actives SPA Experimental Research And Mechanism Of Anti-tumor Effect

ABSTRACTObjectives: SPA, a natural product extracted from algae, was reported have a lot of bioactivities such as, antitumor, and immuno-regulation effect. In order to disscuss the effect of SPA on lung carcinoma and the mechanism, the inhibition of SPA to Lewis lung carcinoma as animal model and the effect on the apoptosis induction of A549 lung carcinoma cells was investigated both in vitro and in vivo.Methods: ① The anti-proliferative effects of SPA on A549 lung adeno-carcinoma cells were observed by MTT assay as in vitro cell culture. ② C57BL/6 mice implanted with Lewis lung carcinoma were used as experimental animal model. Three experimental groups received SPA, 20 mg/kg (group 2), 40mg/kg (group 3) or 80 mg/kg (group 4), o.p., after inoculation with Lewis lung carcinoma .The inhibiting activity of SPA to Lewis lung carcinoma as well as specific and non specific immuity and cytokines activity in serum and spleen such as NK cells, IL-1, IL-2 were assayed.③Serum pharmacological method, and both in vivo and in vitro anti-tumor experiments were used in the studies. Proliferation of A549 tumor cells treated with SPA was detected by MTT assay; After incubating A549 and SPA with contained serum at different concentration, the activity of TNF was detected; the growth and apoptosis of cells ,cell cycle and apoptosis rate were observed and detected by Flowcytometric Assay., Results: ① SPA inhibited the growth of implanted Lewis lung carcinoma in vivo significantly and in dose dependent manner .The inhibitory rate of SPA on C57BL mice implanted Lewis lung carcinoma were 35.27%(P<0.01,48.29%(P<0.001),65.41%(P<0.01)respectively, which had dose-dependent effects ②SPA significantly increased the weight of thymus and the levels of serum specific antibody hemolysin .The phagocytic activities of the peritoneal macrophages in mice and the reaction of DTH were higer than the control group.. In addition, induction of IL-1,IL-2,NK activity in implanted mice was also increased..③SPA directly adding to their cultured medium neither induced A549 lung cancer cell apoptosis nor inhibited its proliferation in vitro.④)Drug-contained serum significantly induced A549 lung cancer cell apoptosis and inhibited its proliferation, showing time and dose-dependent relationship. The level of TNFα was also higher than the control group.Conclusion : SPA possessed remarkable inhibitory activity against lung neoplasia animal models and lung cancer cell strain. .SPA can increase the specific and non-specific activity of immune system and induce the production of cytokines. It was indicated that antitumor effects of SPA may be related to the immuno-enhancing activities.The anti tumor activity of the drug was considered to be derived from apoptosis induction ,which might be associated with the immuno-modulated activity .