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纳库巴碱通过体内外诱导细胞凋亡抑制人肝癌生长。

Noscapine inhibits human hepatocellular carcinoma growth through inducing apoptosis in vitro and in vivo.

出版信息

Neoplasma. 2016;63(5):726-33. doi: 10.4149/neo_2016_509.

DOI:10.4149/neo_2016_509
PMID:27468876
Abstract

Noscapine, a phthalideisoquinoline alkaloid derived from opium, has been demonstrated as a promising anti-tumor compound against various cancers. However, the anti-cancer activity of noscapine in hepatocellular carcinoma has not been defined. In this study, we investigate the inhibitive effects of noscapine on human hepatocellular carcinoma (HCC) using both in vitro and in vivo models. In vitro proliferation assay showed that noscapine suppressed HepG2 and Huh7 cells in dose- and time-dependent manners. With a mouse xenograft model, noscapine showed notable inhibition on HCC tumor growth in vivo without suppression of body weight. Moreover, apoptotic induction and regulation of related signalings by noscapine were examined by nuclear DNA staining, TUNEL, and western blotting assays. Results showed that noscapine induced apoptosis in HCC cells both in vitro and in vivo. Further studies indicated that noscapine induced antive-capsase-3, cleavage PARP, and decreased the ratio of Bcl-2/Bax. Hence, these data indicates that noscapine selectively suppresses HCC cell growth through apoptosis induction, providing evidence for application of noscapine as a novel agent against human hepatocellular carcinoma.

摘要

那可丁,一种源自鸦片的苯酞异喹啉生物碱,已被证明是一种有前途的抗肿瘤化合物,可对抗多种癌症。然而,那可丁在肝细胞癌中的抗癌活性尚未确定。在这项研究中,我们使用体外和体内模型研究了那可丁对人肝癌(HCC)的抑制作用。体外增殖实验表明,那可丁以剂量和时间依赖的方式抑制 HepG2 和 Huh7 细胞。在小鼠异种移植模型中,那可丁在体内显著抑制 HCC 肿瘤生长,而体重无下降。此外,通过核 DNA 染色、TUNEL 和 Western blot 检测研究了那可丁诱导的凋亡和相关信号通路的调节。结果表明,那可丁在体外和体内诱导 HCC 细胞凋亡。进一步的研究表明,那可丁诱导抗 caspase-3、裂解 PARP,并降低 Bcl-2/Bax 的比值。因此,这些数据表明,那可丁通过诱导细胞凋亡选择性地抑制 HCC 细胞生长,为将那可丁作为一种新型抗人肝癌药物的应用提供了证据。

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