Cancer Epidemiology, 2012, 36: e387–e393.

Inhibitory effect of genistein on the invasive potential of human cervical cancer cells via modulation of matrix metalloproteinase-9 and tissue inhibitiors of matrix metalloproteinase-1 expression

Arif Hussain, Geetganga Harish, et al

Department of Biotechnology, Manipal University, P.O. Box 345050, Dubai, United Arab Emirates; et al

Background: One of the most challenging stumbling blocks for the treatment of cancer is the ability of cancer cells to break the natural barriers and spread from its site of origin to non-adjacent regional and distant sites, accounting for high cancer mortality rates. Gamut experimental and epidemiological data advocate the use of pharmacological or nutritional interventions to inhibitor delay various stage(s) of cancer such as invasion and metastasis. Genistein, a promising chemopreventive agent, has gained considerable attention for its powerful anti-carcinogenic, anti-angiogenic and chemosensitizing activities.

Methods: In this study, the cytotoxic potential of genistein on HeLa cells by cell viability assay and the mode of cell death induced by genistein were determined by nuclear morphological examination, DNA laddering assay and cell cycle analysis. Moreover, to establish its inhibitory effect on migration of HeLa cells, scratch wound assay was performed and these results were correlated with the expression of genes involved in invasion and migration (MMP-9 and TIMP-1) by RT-PCR.

Results: The exposure of HeLa cells to genistein resulted in significant dose- and time-dependent growth inhibition, which was found to be mediated by apoptosis and cell cycle arrest at G2/M phase. In addition, it induced migration-inhibition in a time-dependent manner by modulating the expression of MMP-9 and TIMP-1.

Conclusion: Our results signify that genistein may be an effective anti-neoplastic agent to prevent cancer cell growth and invasion and metastasis. Therefore therapeutic strategies utilizing genistein could be developed to substantially reduce cancer morbidity and mortality.

荷兰《癌症流行病学》，2012年12月

金雀异黄素通过调解基质金属蛋白酶-9 及基质金属蛋白酶-1 表达的组织抑制剂来抑制人体宫颈癌细胞的侵袭潜能

阿里夫  侯赛因，盖特冈亚 哈里什等

阿拉伯联合酋长国迪拜马尼帕尔大学生物工程系等

背景︰癌症治疗最具挑战性的一点是癌症细胞打破自然壁垒，从原生位扩散转移到非相邻区域和较远区域的能力，是癌症死亡率高的重要原因。色域实验和流行病学数据提倡使用药物或营养干预的措施抑制延迟癌症侵袭和转移等各种阶段。金雀异黄素，是一种有前途的化学预防药物，受到了相当大的重视，因为其强大的抗癌变、 抗血管生成和化学增敏活性。

方法︰ 本研究中，金雀异黄素对 HeLa 细胞的细胞毒性潜力和诱导细胞死亡的模式通过细胞核形态学检查，DNA 阶梯式检测及细胞周期分析来检测。而且，为确认其对 HeLa 细胞迁移的抑制作用，进行划痕损伤实验，并且将这些结果与通过逆转录-聚合酶链反应入侵和迁移 （基质金属蛋白酶-9 和 TIMP-1） 的基因表达联系在一起。

结果︰ 接触金雀异黄素的 HeLa 细胞表现出明显的剂量和时间依赖性生长抑制，可以在 G2/M 期介导细胞的凋亡和细胞周期阻滞。此外，它还通过调节基质金属蛋白酶-9 和TIMP-1 的表达，以时间依赖性的方式诱导迁移抑制。

结论︰ 我们的结果表明，金雀异黄素可能是有效的抗肿瘤药物以防止肿瘤细胞的生长、侵袭和转移。因此可以开发使用金雀异黄素的治疗策略，极大地降低癌症发病率和死亡率。