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竹节香附素 A 诱导人胃癌细胞凋亡并抑制其体外侵袭。

Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro.

机构信息

Department of Oncology, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Biochem Biophys Res Commun. 2013 Sep 20;439(2):196-202. doi: 10.1016/j.bbrc.2013.08.060. Epub 2013 Aug 27.

DOI:10.1016/j.bbrc.2013.08.060
PMID:23988447
Abstract

Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A's dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug.

摘要

白头翁皂苷 A 是草药白头翁中一种三萜皂苷,据报道它能抑制肝癌和肺癌细胞的生长。然而,人们对其在胃癌 (GC) 细胞中的作用知之甚少。本研究旨在探讨其在体外对三种不同分化阶段 GC 细胞 (BGC-823、SGC-7901 和 MKN-28) 的抑制作用及其可能的机制。增殖试验和流式细胞术分别表明白头翁皂苷 A 具有剂量依赖性的抑制作用,并确定了其诱导细胞凋亡的作用。Transwell 试验、划痕愈合试验和细胞基质黏附试验表明,白头翁皂苷 A 能显著抑制 BGC-823 细胞的侵袭、迁移和黏附能力。此外,实时定量 PCR 和 Western blot 分析发现,白头翁皂苷 A 增加了 Bax 的表达,同时降低了 Bcl-2、Bcl-xL 和 Survivin 的表达,并显著激活了 caspase-3、caspase-8、caspase-9 和多聚 ADP 核糖聚合酶 (PARP)。此外,白头翁皂苷 A 还能上调富含半胱氨酸的 Kazal 基序的反转诱导蛋白 (RECK)、E-钙黏蛋白 (E-cad) 的表达,下调基质金属蛋白酶-2 (MMP-2)、MMP-9、MMP-14 和 Rhoc 的表达。综上所述,白头翁皂苷 A 抑制人 GC 细胞的增殖,诱导其凋亡,并抑制侵袭、迁移和黏附能力,具有成为抗肿瘤药物的潜力。

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