genistein多途径抑制乳腺癌细胞生长和侵袭

Genistein exerts multiple suppressive effects on human breast carcinoma cells

目的 研究genistein在乳腺癌细胞生长和侵袭中的作用。方法 应用体外细胞培养和体内乳腺癌细胞移植裸鼠模型以及酶谱分析、Northern和Westernblot方法。结果 在体外实验中 ,genistein不仅具有抑制乳腺癌细胞生长的作用 ,还具有抑制乳腺癌细胞侵袭的功能 ,这种抑制功能是伴随genistein能明显抑制蛋白金属酶MMP 9的表达和增加组织金属蛋白酶抑制剂TIMP1的表达。genistein能明显抑制MDA MB 2 31和MCF 7乳腺癌细胞的裸鼠移植肿瘤的生长 ,而这种肿瘤生长抑制作用是伴随着genistein明显增加体内乳腺癌移植肿瘤的p2 1WAF1/CIP1mRNA和蛋白水平的表达以及肿瘤细胞的细胞凋亡的产生。同时genistein也能明显抑制MDA MB 2 31和MCF 7乳腺癌细胞的裸鼠移植肿瘤的血管生成 ,并明显抑制移植肿瘤和裸鼠周围血液中的VEGF和TGF β1的水平。 结论genistein化学预防乳腺癌很可能是多途径的机制 ,同时也为genistein在今后治疗乳腺癌的临床应用提供了实验依据。

Objective To study the suppressive effects of genistein on progression of breast carcinoma.Methods In vitro cell culture, animal studies, zymography, Northern and Western blot were used in this study. Results Genistein inhibited in vitro invasion of MCF 7 and MDA MB 231 cells. This inhibition was associated with down regulation of MMP 9 and up regulation of TIMP 1. These effects were also demonstrated in vivo. Genistein inhibited growth of the breast cancer cells transplanted in nude mice. The growth inhibitory effect was associated with increased tumor cell apoptosis, and up regulated p21WAF1/CIP1 expression. Furthermore, genistein inhibited angiogenesis as shown by decreased vessel density and decreased production and release of VEGF and TGF β1.Conclusion Genistein exerts multiple suppressive effects on breast carcinoma. It may help halt its progression.