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穿心莲内酯通过下调 PI3 激酶/Akt 信号通路抑制骨桥蛋白表达和乳腺癌生长。

Andrographolide inhibits osteopontin expression and breast tumor growth through down regulation of PI3 kinase/Akt signaling pathway.

机构信息

National Center for Cell Science, NCCS Complex, Pune 411 007, India.

出版信息

Curr Mol Med. 2012 Sep;12(8):952-66. doi: 10.2174/156652412802480826.

DOI:10.2174/156652412802480826
PMID:22804248
Abstract

Breast cancer is one of the most common cancers among women in India and around the world. Despite recent advancement in the treatment of breast cancer, the results of chemotherapy to date remain unsatisfactory, prompting a need to identify natural agents that could target cancer efficiently with least side effects. Andrographolide (Andro) is one such molecule which has been shown to possess inhibitory effect on cancer cell growth. In this study, Andro, a natural diterpenoid lactone isolated from Andrographis paniculata has been shown to inhibit breast cancer cell proliferation, migration and arrest cell cycle at G2/M phase and induces apoptosis through caspase independent pathway. Our experimental evidences suggest that Andro attenuates endothelial cell motility and tumor-endothelial cell interaction. Moreover, Andro suppresses breast tumor growth in orthotopic NOD/SCID mice model. The anti-tumor activity of Andro in both in vitro and in vivo model was correlated with down regulation of PI3 kinase/Akt activation and inhibition of pro-angiogenic molecules such as OPN and VEGF expressions. Collectively, these results demonstrate that Andro may act as an effective anti-tumor and anti-angiogenic agent for the treatment of breast cancer.

摘要

乳腺癌是印度和全球女性中最常见的癌症之一。尽管乳腺癌的治疗最近取得了进展,但迄今为止化疗的结果仍不尽如人意,因此需要确定能够有效靶向癌症且副作用最小的天然药物。穿心莲内酯(Andro)就是这样一种分子,它已被证明对癌细胞生长具有抑制作用。在这项研究中,从穿心莲中分离得到的天然二萜内酯穿心莲内酯已被证明可抑制乳腺癌细胞增殖、迁移,并将细胞周期阻滞在 G2/M 期,通过 caspase 非依赖性途径诱导细胞凋亡。我们的实验证据表明,穿心莲内酯可减弱内皮细胞的迁移和肿瘤内皮细胞的相互作用。此外,穿心莲内酯还可抑制原位 NOD/SCID 小鼠模型中的乳腺肿瘤生长。在体外和体内模型中,穿心莲内酯的抗肿瘤活性与下调 PI3 激酶/Akt 激活以及抑制促血管生成分子(如 OPN 和 VEGF 的表达)相关。综上所述,这些结果表明,穿心莲内酯可能是一种有效的抗肿瘤和抗血管生成药物,可用于治疗乳腺癌。

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