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白藜芦醇类似物4,4'-二羟基反式芪能有效抑制癌症侵袭和转移。

Resveratrol analogue 4,4'-dihydroxy-trans-stilbene potently inhibits cancer invasion and metastasis.

作者信息

Savio Monica, Ferraro Daniela, Maccario Cristina, Vaccarone Rita, Jensen Lasse D, Corana Federica, Mannucci Barbara, Bianchi Livia, Cao Yihai, Stivala Lucia Anna

机构信息

Department of Molecular Medicine, Immunology and General Pathology Unit, University of Pavia, Pavia, Italy.

Department of Biology and Biotechnology, Comparative Anatomy and Citology Laboratory, University of Pavia, Pavia, Italy.

出版信息

Sci Rep. 2016 Feb 1;6:19973. doi: 10.1038/srep19973.

Abstract

We investigated the preventive effects of resveratrol analogue 4,4'-dihydroxy-trans-stilbene (DHS) on cancer invasion and metastasis. Two different in vivo approaches of mouse and zebrafish lung cancer invasion models were employed in our study. The in vitro results showed that DHS displays potent inhibition on anchorage-dependent or -independent cell growth of LLC cells, leading to impairment of the cell cycle progression with reduction of cell numbers arresting at the G1 phase, an evident accumulation of pre-G1 events correlated with apoptotic behaviour. In addition, DHS induces a marked inhibition of LLC cell migration and matrigel invasion. In a murine lung cancer model, tumour volume, cell proliferation, and tumour angiogenesis were significantly inhibited by DHS. Importantly, liver metastatic lesions were significantly reduced in DHS-treated mice. Similarly, DHS significantly inhibits lung cancer cell dissemination, invasion and metastasis in a zebrafish tumour model. These findings demonstrate that DHS could potentially be developed as a novel therapeutic agent for treatment of cancer and metastasis.

摘要

我们研究了白藜芦醇类似物4,4'-二羟基反式芪(DHS)对癌症侵袭和转移的预防作用。在我们的研究中采用了小鼠和斑马鱼肺癌侵袭模型这两种不同的体内实验方法。体外实验结果表明,DHS对LLC细胞的贴壁依赖性或非贴壁依赖性细胞生长具有强大的抑制作用,导致细胞周期进程受损,G1期停滞的细胞数量减少,G1期前事件明显积累,这与凋亡行为相关。此外,DHS显著抑制LLC细胞迁移和基质胶侵袭。在小鼠肺癌模型中,DHS显著抑制肿瘤体积、细胞增殖和肿瘤血管生成。重要的是,在接受DHS治疗的小鼠中,肝转移灶明显减少。同样,在斑马鱼肿瘤模型中,DHS显著抑制肺癌细胞的播散、侵袭和转移。这些发现表明,DHS有可能被开发为一种治疗癌症和转移的新型治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0310/4734289/e031b4722cc9/srep19973-f1.jpg

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