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抗癌肽CB1a对单个肺癌细胞的疗效验证及显微镜观察

Efficacy verification and microscopic observations of an anticancer peptide, CB1a, on single lung cancer cell.

作者信息

Kao Feng-Sheng, Pan Yun-Ru, Hsu Ray-Quen, Chen Hueih-Min

机构信息

National Nano Device Laboratories, Nano Biomedical Group, Hsinchu, Taiwan.

出版信息

Biochim Biophys Acta. 2012 Dec;1818(12):2927-35. doi: 10.1016/j.bbamem.2012.07.019. Epub 2012 Jul 28.

Abstract

In this work, we introduce a new customized anti-lung cancer peptide, CB1a, with IC₅₀ of about 25.0 ± 1.6 μM on NCI-H460 lung cancer cells. Using a multi-cellular tumor spheroid (MCTS) model, results show that CB1a is potent in preventing the growth of lung cancer tumor-like growths in vitro. Additionally, atomic force microscopy (AFM) was used to examine cell surface damage of a single cancer. The mechanism for cell death under CB1a toxicity was verified as being largely due to cell surface damage. Moreover, with a treatment dosage of CB1a at 25 μM, Young's module (E) shows that the elasticity and stiffness of cancer cell decreased with time such that the interaction time for a 50% reduction of E (IT₅₀) was about 7.0min. This new single-cell toxicity investigation using IT₅₀ under AFM assay can be used to separately verify drug efficacy in support of the traditional IC₅₀ measurement in bulk solution. These results could be of special interest to researchers engaged in new drug development.

摘要

在这项工作中,我们引入了一种新的定制抗肺癌肽CB1a,其对NCI-H460肺癌细胞的IC₅₀约为25.0±1.6μM。使用多细胞肿瘤球体(MCTS)模型,结果表明CB1a在体外对肺癌肿瘤样生长的抑制作用显著。此外,利用原子力显微镜(AFM)检测单个癌细胞的表面损伤。CB1a毒性作用下的细胞死亡机制经证实主要是由于细胞表面损伤。而且,当CB1a的处理剂量为25μM时,杨氏模量(E)显示癌细胞的弹性和硬度随时间降低,使得E降低50%的相互作用时间(IT₅₀)约为7.0分钟。这种在AFM检测下使用IT₅₀进行的新的单细胞毒性研究可用于单独验证药物疗效,以支持传统的批量溶液IC₅₀测量。这些结果可能会引起从事新药开发的研究人员的特别兴趣。

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