海藻硫酸多糖对肺癌增殖的抑制作用及其机制

目的　探讨海藻硫酸多糖 (SPA)对肺癌增殖的抑制作用及其可能的机制。方法(1)建立Lewis肺癌小鼠模型 ,以抽签法随机分为对照组 ,SPA 2 0、4 0、80mg/kg组及替加氟 (FT 2 0 7)组 ,每组 10只 ,从接种肿瘤次日开始分别灌服生理盐水 ,SPA 2 0、4 0、80mg/kg及FT 2 0 715 0mg/kg ,连续 10d。末次给药后 2 4h处死小鼠 ,剥取肿瘤 ,称瘤重 ,计算抑瘤率。同时应用体外细胞培养模型 ,采用甲基噻唑基四唑 (MTT)法检测SPA在体外对肺癌细胞增殖的影响。 (2 )取雄性新西兰兔 6只 ,按抽签法随机分为对照组、SPA组及环磷酰胺 (CTX)组 ,分别口服生理盐水、SPA 5 0 0mg/kg、CTX 10 0mg/kg,连续10d。最后 1次灌药后 2h ,采集含药血清 ,通过流式细胞仪观察SPA及其含药血清对A5 4 9肺癌细胞增殖、凋亡、细胞周期以及凋亡相关基因p5 3、bcl 2的影响。结果　 (1) 2 0、4 0、80mg/kgSPA连续灌服给药 10d ,对小鼠Lewis肺癌的生长具有明显抑制作用 ,抑制率分别为 35 .2 7%、4 8.2 9%和 6 5 .4 1%。体外SPA在 2 5～ 10 0 μg/ml范围内对A5 4 9肺癌细胞生长无明显抑制作用 (P >0 .0 5 )。 (2 )含SPA兔血清在体外可明显抑制肺癌细胞增殖、诱导癌细胞凋亡 ,出现明显的细胞周期阻滞。A5 4 9细胞株经含SPA兔血清作用后 ,p5 3阳性蛋白标记

Therapeutic effect and mechanism of sulfate polysacchride of algae on lung cancer

OBJECTIVE: To study the effect of sulfate polysaccharide of algae (SPA) on lung carcinoma and it's mechanism. METHODS: (1) C57BL/6 mice implanted with Lewis lung carcinoma were used as experimental animal model. The mice were randomly divided into a control group, SPA groups (3 groups) and a FT-207 group. After inoculation with Lewis lung carcinoma, the control group was treated with NS, the 3 SPA groups were treated with SPA 20 mg, 40 mg, and 80 mg/kg respectively, and the FT-207 group with FT-207 150 mg/kg for 10 days. The inhibiting activity of SPA on Lewis lung carcinoma was assayed, and proliferation of A549 tumor cells treated with SPA was detected by MTT assay. (2) New Zealand rabbits were randomly divided into a control group, a SPA 500 mg/kg group and a CTX 100 mg/kg group. Serum pharmacological method, and both in vivo and in vitro anti-tumor experiments were used in the study. After incubating A549 with SPA containing serum at different concentrations, the growth and apoptosis of cells, cell cycle, apoptosis rate and expression of apoptosis associated genes such as p53 and bcl-2 were detected by flow-cytometric assay. RESULTS: (1) SPA significantly inhibited the growth of implanted Lewis lung carcinoma in vivo and the effect had a dose dependent manner. The inhibitory rates of SPA on C57BL mice implanted Lewis lung carcinoma were 35.27% (P < 0.01), 48.29% (P < 0.01), and 65.41% (P < 0.01) respectively, which showed dose-dependent effects. SPA directly added to the culture medium neither induced A549 lung cancer cell apoptosis nor inhibited its proliferation in vitro. (2) SPA containing serum significantly induced A549 lung cancer cell apoptosis and inhibited its proliferation, with an increased expression of p53 and decreased expression of bcl-2 positive proteins, showing time and dose-dependent relationship. CONCLUSIONS: SPA possessed remarkable inhibitory activity against lung neoplasia in animal models and lung cancer cell strain. The anti tumor activity of SPA was considered to be derived from apoptosis induction, which might be associated with the increased expression of p53 and decreased expression of bcl-2 positive proteins.