The algal polysaccharide ulvan suppresses growth of hepatoma cells
The algal polysaccharide ulvan suppresses growth of hepatoma cells
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藻多糖绿藻硫化多糖抑制肝癌细胞生长
作者：
Zhao C;Lin G;Wu D;Liu D;You L;Hogger P;Simal-Gandara J;Wang M;da Costa JGM;MARUNAKA Y;Daglia M;Khan H;Filosa R;Wang S;Xiao J
肿瘤的治疗依赖于宿主的免疫系统。分别在H22荷瘤小鼠和环磷酰胺诱导的免疫抑制小鼠中评价了石莼多糖（ULP）的抗肿瘤和免疫调节活性。通过多角度激光散射、高效液相色谱、傅立叶变换红外和核磁共振鉴定ULP的结构性质。它由α-D-Manp-（1→，→ 2，4）-β-L-Rhap-（1→，β-D-GlcpA-（1→，β-GalpA-（1→，→ 2，4）-α-D-Glcp-（1→，和→6）-β-D-Galp-（1→组成，分子量为1.46 × 105 Da。测定其抗氧化、抗炎和抗肿瘤作用。收集肝脏和肿瘤组织进行组织病理学、免疫组织化学和蛋白质印迹分析。ULP对肿瘤生长的抑制率为74.41%，而环磷酰胺对肿瘤生长有明显的抑制作用。ULP通过增强p53的表达抑制肿瘤的发生，促进IKK α的活化，抑制NF-κ B通路中p65的活化。ULP通过下调PI 3 K/Akt和mTOR的表达，提高BAX/Bcl-2比值，抑制肿瘤生长。抑制TRAF 2/TNF-α和CD 31/VEGF分别实现了对肿瘤细胞的直接杀伤作用和通过抑制血管生成抑制肿瘤增殖。ULP还能增加免疫球蛋白M和总超氧化物歧化酶的水平，降低甲烷二甲醛的水平，抑制PI 3 K/AKT/mTOR/p70 S6 k通路的激活。结果表明，ULP具有明显的抗肿瘤活性和免疫调节作用。
Treatment for tumors depends on host immune system. The antitumor and immunoregulatory activities ofUlva lactucapolysaccharide (ULP) were evaluated in H22 tumor‐bearing mice and cyclophosphamide‐induced immunosuppressed mice, respectively. The structural properties of ULP were identified through multi‐angle laser light scattering, high‐performance liquid chromatography, Fourier‐transformed infrared, and nuclear magnetic resonance. It was composed of α‐D‐Manp‐(1→, →2,4)‐β‐L‐Rhap‐(1→, β‐D‐GlcpA‐(1→, β‐GalpA‐(1→, →2,4)‐α‐D‐Glcp‐(1→, and →6)‐β‐D‐Galp‐(1→ with the molecular weight of 1.46 × 105Da. Its antioxidant, anti‐inflammatory, and antitumor effects were determined. Liver and tumor tissues were collected for histopathological, immunohistochemical, and western blotting analysis. ULP showed the great tumor growth inhibition of 74.41% compared with cyclophosphamide, which has side effects on immune system. ULP enhanced the expression ofp53to inhibit tumorigenesis, promoted the activation ofIKKα, and inhibited the activation ofp65within theNF‐κBpathway. ULP inhibited the tumor growth through downregulating the expressions ofPI3K/AktandmTOR, and promotingBAX/Bcl‐2ratio. The inhibition ofTRAF2/TNF‐αandCD31/VEGFachieved a direct killing effect on tumor cells and inhibited tumor proliferation by inhibiting angiogenesis, respectively. Moreover, ULP increased the levels of immunoglobulin M and total superoxide dismutase, decreased the level of methane dicarboxylic aldehyde, and inhibited the activation ofPI3K/AKT/mTOR/p70S6kpathways. The results showed that ULP exhibited pronounced antitumor activity and immunoregulatory effect.