Flavonoid ampelopsin inhibits the growth and metastasis of prostate cancer in vitro and in mice.

Flavonoid ampelopsin inhibits the growth and metastasis of prostate cancer in vitro and in mice.
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DOI:
10.1371/journal.pone.0038802
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Zhou JR
Zhou JR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ni F;Gong Y;Li L;Abdolmaleky HM;Zhou JR

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本研究的目的是评价一种新的黄酮类化合物蛇葡萄素(AMP)对前列腺癌细胞生长和转移的化学预防作用。AMP在体外抑制雄激素敏感性LNCaP增殖方面表现出更有效的活性,在较小程度上抑制雄激素非依赖性PC-3人前列腺癌细胞系的增殖,主要是通过诱导与bcl-2下调相关的凋亡。另一方面,AMP对正常前列腺上皮细胞增殖的抑制活性远低于对前列腺癌细胞系的抑制活性。AMP还抑制PC-3细胞在体外的迁移和侵袭,与下调CXCR 4表达有关。在使用原位前列腺肿瘤模型的动物研究中,AMP(150和300 mg/kg体重)以剂量依赖性方式抑制PC-3肿瘤的生长以及淋巴结和肺转移。与对照组小鼠相比,AMP 300 mg/kg BW治疗组小鼠的最终肿瘤重量减少了49.2%(P<0.05),淋巴结转移减少了54.5%(P = 0.3),肺转移减少了93%(P<0.05),但摄食量和体重没有明显变化。  AMP的体内抗生长和抗转移活性与诱导前列腺癌细胞凋亡和抑制前列腺癌细胞增殖、减少前列腺肿瘤血管生成和减少CXCR 4表达相关。我们的研究结果提供了支持性证据,以保证进一步研究开发AMP作为一种新的有效和安全的候选药物,对前列腺癌的进展和转移。
The objective of this study was to evaluate the chemopreventive effect of a novel flavonoid, ampelopsin (AMP) on the growth and metastasis of prostate cancer cells. AMP showed the more potent activity in inhibiting the proliferation of androgen-sensitive LNCaP and, to less extent, androgen-independent PC-3 human prostate cancer cell lines in vitro, primarily by induction of apoptosis associated with down-regulation of bcl-2. On the other hand, AMP showed much less activity in inhibiting the proliferation of normal prostate epithelial cells than that of prostate cancer cell lines. AMP also inhibited the migration and invasion of PC-3 cells in vitro associated with down-regulation of CXCR4 expression. In the animal study using an orthotopic prostate tumor model, AMP (150 and 300 mg/kg body weight) inhibited the growth of PC-3 tumors and lymph node and lung metastases in a dose-dependent manner. Compared to the control mice, mice treated with AMP at 300 mg/kg BW had reduced final tumor weight by 49.2% (P<0.05), lymph node metastases by 54.5% (P = 0.3) and lung metastases by 93% (P<0.05), but had no apparent alteration on food intake or body weight. The in vivo anti-growth and anti-metastasis activities of AMP were associated with induction of apoptosis and inhibition of proliferation of prostate cancer cells, reduction of prostate tumor angiogenesis, and reduction of CXCR4 expression. Our results provide supporting evidence to warrant further investigation to develop AMP as a novel efficacious and safe candidate agent against progression and metastasis of prostate cancer.
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