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OSW-1通过在体外和体内诱导凋亡对结肠癌具有有效的细胞毒性活性。

Effective cytotoxic activity of OSW-1 on colon cancer by inducing apoptosis in vitro and in vivo.

作者信息

Zhang Yanhong, Fang Fengqi, Fan Kai, Zhang Yanli, Zhang Jie, Guo Huishu, Yu Peiyao, Ma Jianmei

机构信息

Graduate School of Dalian Medical University, Dalian, Liaoning 116044, P.R. China.

The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.

出版信息

Oncol Rep. 2017 Jun;37(6):3509-3519. doi: 10.3892/or.2017.5582. Epub 2017 Apr 19.

Abstract

As a natural compound, Ornithogalum caudatum Ait is primarily used as an anti-inflammatory and antitumor agent in Chinese folk medicine. In 1992, OSW-1 was isolated from this compound, which is a new member of cholestane saponin family. In numerous recent studies, OSW-1 has been shown to have powerful cytotoxic anticancer effects against various malignant cells. However, the therapeutic efficacy of OSW-1 on colon cancer and the underlying mechanism are not understood. To explore the mechanism underlying OSW-1 in antitumor therapy, a therapeutic function analysis of OSW-1 on colon cancer was performed in vitro and in vivo. It was shown that with low toxicity on normal colonic cells, OSW-1 suppresses colon cancer cells in vitro and this inhibition was via the intrinsic apoptotic pathway, which increased cellular calcium, changed mitochondrial membrane potential, disrupted mitochondrial morphology, and led to the release of cytochrome c and the activation of caspase-3. Furthermore, in a nude mouse model, OSW-1 had a powerful effect on suppressing colon tumor proliferation without significant side effects through the apoptosis pathway. Taken together, these results demonstrate that OSW-1 is a potential drug for colon cancer treatment.

摘要

作为一种天然化合物,虎眼万年青在中国民间医学中主要用作抗炎和抗肿瘤药物。1992年,从该化合物中分离出OSW-1,它是胆甾烷皂苷家族的新成员。在最近的众多研究中,OSW-1已被证明对各种恶性细胞具有强大的细胞毒性抗癌作用。然而,OSW-1对结肠癌的治疗效果及其潜在机制尚不清楚。为了探究OSW-1在抗肿瘤治疗中的潜在机制,我们在体外和体内对OSW-1对结肠癌的治疗作用进行了分析。结果表明,OSW-1对正常结肠细胞毒性较低,在体外可抑制结肠癌细胞,且这种抑制作用是通过内源性凋亡途径实现的,该途径增加了细胞内钙含量,改变了线粒体膜电位,破坏了线粒体形态,导致细胞色素c释放并激活了caspase-3。此外,在裸鼠模型中,OSW-1通过凋亡途径对抑制结肠肿瘤增殖具有强大作用,且无明显副作用。综上所述,这些结果表明OSW-1是一种潜在的结肠癌治疗药物。

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