文蛤抗肿瘤多肽的分离纯化及其作用机理的研究
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摘要
恶性肿瘤是严重威胁人类健康的疾病。目前的抗肿瘤药物存在选择性差、毒副作用大等缺点,寻找高效低毒的抗肿瘤药物已经成为当前肿瘤研究的重要内容。近年来,海洋来源的具有抗肿瘤活性物质的研究取得了很多成果,获得了多种高活性、毒副作用小、作用机制新颖的活性化合物,为新型抗肿瘤药物的研发提供了新思路。文蛤又名花蛤,属帘蛤科、Veneridae文蛤属。在我国大部分海域都有分布。
文蛤有清热利湿、化痰、散结的功效,对肝癌有明显的抑制作用。从传统海洋药物文蛤中筛选具有抗肿瘤活性物质,并探讨其抗肿瘤机制,为开发新型抗肿瘤海洋药物提供理论依据与实验基础,并可进一步开发海洋贝类的药用价值。本论文通过离子交换、凝胶过滤等方法从文蛤中提取分离抗肿瘤活性多肽;并通过基质辅助激光解吸技术、电镜技术、流式细胞仪技术,研究了文蛤多肽对人肝癌BEL-7402的增殖作用及体内外抗肿瘤活性作用,探讨了其抗肿瘤作用的机理。通过研究发现文蛤多肽的抗肿瘤作用方式可能是通过改变肿瘤细胞膜通透性,进而破坏微管蛋白聚合、阻滞细胞周期,产生抑制肿瘤细胞增殖的活性。通过裸鼠动物实验发现,该多肽在剂量在25mg/kg、50mg/kg和75mg/kg时的抑瘤率分别为42%、57%和72%(P<0.01)。
Most of current anti-tumor chemotherapies acted against normal mammalian cells, consequently causing severe side effects. So far, literature on natural products derived from marine organisms was characterized by low cytotoxity and new mechanisms. Marine organisms represented essentially unexploited resources for producing of potentially biological and pharmacological important natural drug leads. Meretrix Meretrix (Meretrix, Veneridae) was a traditional Chinese drug with anti-tumor activities. The aim of this study is to find a novel peptide with anticancer activity from Chinese traditional marine medicine Meretrix Meretrix, and illustrate the mechanism of the peptide. By varieties of chromatographies including ion exchange chromatography, Sephadex gel, an anti-tumor peptide was isolated from the Meretrix Meretrix. Meanwhile, the possible anticancer pharmacological action modes were also investigated by electrophoresis, scanning electron microscopy, cell cycle arrest assay, and so on. Anti-tumor effect of Meretrix Meretrix anticancer peptide approach may be by altering the tumor cell membrane permeability, thereby undermining tubulin polymerization, blocking cell cycle, resulting in inhibition of tumor cell proliferation activity. Meretrix Meretrix anticancer peptide transplanted into nude mice of human hepatoma BEL-7402 role of 25mg/kg, 50mg/kg and 75mg/kg inhibition rate are 42%, 57% and 72% (P<0.01), respectively.
文蛤有清热利湿、化痰、散结的功效,对肝癌有明显的抑制作用。从传统海洋药物文蛤中筛选具有抗肿瘤活性物质,并探讨其抗肿瘤机制,为开发新型抗肿瘤海洋药物提供理论依据与实验基础,并可进一步开发海洋贝类的药用价值。本论文通过离子交换、凝胶过滤等方法从文蛤中提取分离抗肿瘤活性多肽;并通过基质辅助激光解吸技术、电镜技术、流式细胞仪技术,研究了文蛤多肽对人肝癌BEL-7402的增殖作用及体内外抗肿瘤活性作用,探讨了其抗肿瘤作用的机理。通过研究发现文蛤多肽的抗肿瘤作用方式可能是通过改变肿瘤细胞膜通透性,进而破坏微管蛋白聚合、阻滞细胞周期,产生抑制肿瘤细胞增殖的活性。通过裸鼠动物实验发现,该多肽在剂量在25mg/kg、50mg/kg和75mg/kg时的抑瘤率分别为42%、57%和72%(P<0.01)。
Most of current anti-tumor chemotherapies acted against normal mammalian cells, consequently causing severe side effects. So far, literature on natural products derived from marine organisms was characterized by low cytotoxity and new mechanisms. Marine organisms represented essentially unexploited resources for producing of potentially biological and pharmacological important natural drug leads. Meretrix Meretrix (Meretrix, Veneridae) was a traditional Chinese drug with anti-tumor activities. The aim of this study is to find a novel peptide with anticancer activity from Chinese traditional marine medicine Meretrix Meretrix, and illustrate the mechanism of the peptide. By varieties of chromatographies including ion exchange chromatography, Sephadex gel, an anti-tumor peptide was isolated from the Meretrix Meretrix. Meanwhile, the possible anticancer pharmacological action modes were also investigated by electrophoresis, scanning electron microscopy, cell cycle arrest assay, and so on. Anti-tumor effect of Meretrix Meretrix anticancer peptide approach may be by altering the tumor cell membrane permeability, thereby undermining tubulin polymerization, blocking cell cycle, resulting in inhibition of tumor cell proliferation activity. Meretrix Meretrix anticancer peptide transplanted into nude mice of human hepatoma BEL-7402 role of 25mg/kg, 50mg/kg and 75mg/kg inhibition rate are 42%, 57% and 72% (P<0.01), respectively.
引文
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