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J Dairy Sci:牛奶中一种肽片段能杀死胃癌细胞

来源:生物谷 2013-11-10 14:45

2013年11月10日讯 /生物谷BIOON/--近日,台湾研究人员完成一项新研究表明,来自牛奶的一种肽片段--铁蛋白素B25(LFcinB25)对实验室培养的人源胃癌细胞表现出强大的抗癌能力。

这项研究结果发表在Journal of Dairy Science杂志上,提示LFcinB25未来作为胃癌潜在治疗剂的可能性。

Wei-Jung Chen博士说:胃癌是全球癌症相关死亡最常见的原因之一,尤其是在亚洲国家。一般来说,胃癌主要疗法是手术、化疗,如果在早期阶段胃癌就被诊断,治疗一般都是成功的。但现在,迫切需要一种新的治疗策略,可以改善患者的预后。

研究人员评估来自铁蛋白素B的三个肽片段对胃癌细胞的影响,铁蛋白素B是牛奶中具有抗菌性能的肽。三个肽片段中只有一个片段,LFcinB25能以剂量依赖和时间依赖的方式降低人源AGS(胃腺癌)细胞的生存期。

在显微镜下,研究者可以看到,胃癌细胞暴露于LFcinB25下一小时后,LFcinB25迁移至AGS细胞的细胞膜中,在暴露24小时之内,癌细胞的大小已缩小,失去了其附着能力。

在暴露的早期阶段,LFcinB25同时通过细胞凋亡(程序性细胞死亡)和自噬降低细胞的存活率,在暴露后期阶段,细胞凋亡似乎占据主导地位,其机制可能通过caspase依赖性机制,而自噬效应减弱。

这项研究还提出了一个新的治疗靶标--Beclin-1,Beclin-1可提高LFcinB25的细胞毒作用。Beclin-1是一种蛋白质,在细胞自噬、肿瘤生长和神经元变性中起着核心作用。在这项研究中,研究者发现,活化型Beclin-1能增加LFcinB25时间依赖性降低人源AGS (胃腺癌)细胞生存期的功效,作者建议在药物开发过程中,可以利用Beclin-1提高LFcinB25的抗癌效果。

Chen博士总结:应使用各种策略优化LFcinB,以进一步加强其选择性,产生新型抗癌药物,用于治疗胃癌。(生物谷Bioon.com)

Bovine lactoferricin B induces apoptosis of human gastric cancer cell line AGS by inhibition of autophagy at a late stage

W.-R. Pan, P.-W. Chen, Y.-L. S. Chen, H.-C. Hsu, C.-C. Lin, and W.-J. Chen

Gastric cancer is one of the most common malignant cancers, with poor prognosis and high mortality rates worldwide. Therefore, development of an effective therapeutic method without side effects is an urgent need. It has been reported that cationic antimicrobial peptides can selectively bind to negatively charged prokaryotic and cancer cell membranes and exert cytotoxicity without causing severe drug resistance. In the current study, we prepared a series of peptide fragments derived from bovine lactoferrin and evaluated their anticancer potency toward the gastric cancer cell line AGS. Cell viability assay revealed that a 25-AA peptide fragment, lactoferricin B25 (LFcinB25), exhibited the most potent anticancer capability against AGS cells. Lactoferricin B25 selectively inhibited AGS cell growth in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) value of 64 μM. Flow cytometry showed a notable increment of the sub-G1 populations of the cell cycle, indicating the induction of apoptosis by LFcinB25. Western blot analysis further revealed that upon LFcinB25 treatment for 2 to 6 h, apoptosis-related caspases-3, 7, 8, 9, and poly(ADP-ribose) polymerase (PARP) were cleaved and activated, whereas autophagy-related LC3-II and beclin-1 were concomitantly increased. Thus, both apoptosis and autophagy are involved in the early stage of LFcinB25-induced cell death of AGS cells. However, upon treatment with LFcinB25 for 12 to 24 h, LC3-II began to decrease, whereas cleaved beclin-1 increased in a time-dependent manner, suggesting that consecutive activation of caspases cleaved beclin-1 to inhibit autophagy, thus enhancing apoptosis at the final stage. These findings provide support for future application of LFcinB25 as a potential therapeutic agent for gastric cancer.

 

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