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异硫氰酸苄酯抑制人肺癌细胞的增殖并诱导保护性自噬

发表时间:2017-06-15  浏览量:75  下载量:33
全部作者: 张其程,潘振华,刘博宁,徐克
作者单位: 天津医科大学总医院,天津市肺癌研究所
摘 要: 目的:天然小分子物质异硫氰酸苄酯(benzyl isothiocyanate,BITC)可以抑制多种肿瘤细胞的增殖,但是其具体作用机制尚不明确。本文就BITC对人肺癌细胞增殖的抑制作用和诱导自噬的情况展开研究。方法:在3株人非小细胞肺癌细胞(A549、H661和SK-MES-1)中,利用细胞存活检测技术(CCK-8)研究BITC对肿瘤细胞增殖的抑制作用;利用吖啶橙(acridine orange,AO)染色、自噬标记蛋白(LC3)的细胞内聚集化检测以及免疫印迹(Western blotting)检测LC3的剪切情况等技术,研究BITC诱导肺癌细胞发生自噬的情况;使用自噬抑制剂及siRNA技术对自噬的具体作用进行研究;利用小鼠肿瘤移植模型研究BITC对肺癌细胞(A549)体内增殖的抑制效果和诱导自噬情况。结果:BITC可以有效抑制肺癌细胞的增殖并诱导自噬;自噬抑制剂3-甲基腺嘌呤(3-methyladenine,3-MA)以及siRNA敲低Atg5可以增强BITC对肺癌细胞增殖的抑制效果;小鼠肿瘤移植模型实验结果显示BITC可以抑制肺癌细胞在体内的增殖,并且诱导肿瘤细胞发生自噬。结论:BITC在体外和体内均可有效抑制人肺癌细胞的增殖,同时诱导自噬,且自噬在其抑制效果中发挥保护作用。
关 键 词: 分子药理学;肺癌;异硫氰酸苄酯;自噬;抗肿瘤活性
Title: Benzyl isothiocyanate inhibits the growth of human lung cancer cells and induces protective autophagy
Author: ZHANG Qicheng, PAN Zhenhua, LIU Boning, XU Ke
Organization: Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital
Abstract: Objective: Benzyl isothiocyanate (BITC) is a natural low-molecular compound with anti-tumor activity. However, the specific mechanism is still not fully understood. We investigated the growth inhibitory effect and autophagy induction of BITC in human lung cancer cells both in vitro and in vivo. Methods: Three kinds of human non-small cell lung cancer cell lines (A549, H661 and SK-MES-1) were tested. Cell growth inhibitory effect of BITC was determined by CCK-8 method. In BITC treated cells, autophagy induction was characterized by acridine orange (AO) staining, the processing of an autophagy marker protein: microtubule-associated protein 1 light chain 3 (LC3), and intracellular aggregation of LC3 into puncta structure. The specific role of induced autophagy in BITC treatment was studied by using autophagy inhibitors and siRNA. In vivo growth inhibition and autophagy induction were examined by A549 xenograft experiments. Results: The data showed that BITC could inhibit the growth of human lung cancer cells. Autophagy was induced in BITC-treated cells. Inhibition of autophagy by using 3-methyladenine (3-MA) and Atg5 knockdown could enhance the inhibitory effect. Xenograft experiments showed that BITC could inhibit the tumor growth and induced autophagy in cancer cells. Conclusion: BITC could inhibit the growth of human lung cancer cell both in vitro and in vivo and induces a protective autophagy response.
Key words: molecular pharmacology; lung cancer; benzyl isothiocyanate; autophagy; anti-tumor activity
发表期数: 2017年6月第11期
引用格式: 张其程,潘振华,刘博宁,等. 异硫氰酸苄酯抑制人肺癌细胞的增殖并诱导保护性自噬[J]. 中国科技论文在线精品论文,2017,10(11):1244-1254.
 
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