PLoS One：黄酮类物质抑制前列腺癌生长和转移

黄酮类化合物（flavonoids）是一类存在于自然界的、具有2-苯基色原酮（flavone）结构的化合物。黄酮类化合物在植物体中通常与糖结合成苷类，小部分以游离态（苷元）的形式存在。绝大多数植物体内都含有黄酮类化合物，它在植物的生长、发育、开花、结果以及抗菌防病等方起着重要的作用。

近年来，黄酮类化合物的抗肿瘤机制逐步得到研究人员重视，如槲皮素的抗肿瘤活性与其抗氧化作用、抑制相关酶的活性、降低肿瘤细胞耐药性、诱导肿瘤细胞凋亡及雌激素样作用等有关；水飞蓟素的抗肿瘤活性与其抗氧化作用、抑制相关酶活性、诱导细胞周期阻滞等有关。

近日，PLoS One刊出的一则研究发现一种新的黄酮类物质蛇葡萄素（Ampelopsin）具有良好的抗肿瘤转移作用。

该研究的目的是评估一种新的类黄酮物质蛇葡萄素对前列腺癌细胞的生长和转移的化学预防作用。研究发现蛇葡萄素对雄激素敏感的LNCaP细胞来说能更有效地抑制肿瘤细胞的增殖，而对雄激素非依赖性的人前列腺癌PC-3细胞株抑制增殖效果不怎么明显，抑制增殖的主要机制为诱导肿瘤细胞凋亡，下调bcl-2等相关蛋白的表达。

另一方面，蛇葡萄素对正常前列腺上皮细胞增殖的抑制影响远小于对前列腺癌细胞株的抑制影响。在体外，蛇葡萄素也抑制PC-3细胞的迁移和侵袭，这与降低肿瘤细胞CXCR4的表达有关。

在动物研究中，研究人员使用原位前列腺肿瘤模型，给予老鼠蛇葡萄素（150和300毫克/千克），结果发现蛇葡萄素能抑制PC-3肿瘤的生长，减少淋巴结和肺转移，并且呈剂量依赖性。与对照组相比，给予300毫克/千克蛇葡萄素治疗的小鼠瘤重减少了49.2％，淋巴结转移减少了54.5％，肺转移减少了93％。在体内蛇葡萄素抗生长和抗转移的药效均与诱导肿瘤细胞凋亡和抑制前列腺癌细胞生长有关，也与减少前列腺肿瘤血管生成有关。研究结果提供有希望将蛇葡萄素开发成一种新的有效和安全的抗前列腺癌转移药物。

doi:10.1371/journal.pone.0038802
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Flavonoid ampelopsin inhibits the growth and metastasis of prostate cancer in vitro and in mice.

Ni F, Gong Y, Li L, Abdolmaleky HM, Zhou JR.

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.