Pharmaceutical Research, 2010, 27(6):1159-68.

FoxM1 is a novel target of a natural agent in pancreatic cancer

Zhiwei Wang, Yiwei Li, et al

Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, 740 HWCRC, 4100 JohnR Street, Detroit, Michigan 48201, USA

PURPOSE: Pancreatic cancer remains the fourth most common cause of cancer-related death in the United States. Therefore, novel strategies for the prevention and/or treatment are urgently needed. Genistein has been found to be responsible for lowering the rate of pancreatic cancer. However, the molecular mechanisms by which genistein elicits its effects on pancreatic cancer cells has not been fully elucidated. Therefore, the purpose of the current study was to elucidate the anti-cancer mechanism(s) of genistein.

METHODS: Multiple molecular techniques, such as Real-time RT-PCR, Western blot analysis, invasion assay, immunofluorescence assay, gene transfection, MTT assay, and Histone/DNA ELISA, were used.

RESULTS: We found that genistein inhibited cell growth accompanied by induction of apoptosis with concomitant attenuation of FoxM1 and its downstream genes, such as survivin, cdc25a, MMP-9, and VEGF, resulting in the inhibition of pancreatic cancer cell invasion. We also found that down-regulation of FoxM1 by siRNA prior to genistein treatment resulted in enhanced cell growth inhibition and induction of apoptosis.

CONCLUSION: This is the first report showing the molecular role of FoxM1 in mediating the biological effects of genistein in pancreatic cancer cells, suggesting that FoxM1 could be a novel target for the treatment of pancreatic cancer.

美国《药学研究》，2010年6月

FoxM1 在胰腺癌中是自然试剂的新靶点

王志伟，李一伟等

美国韦恩州医科大学卡马诺斯癌症研究所病理部

目的︰ 胰腺癌在美国仍然是第四大最常见致死的癌症。因此，迫切需要新的方法来预防和/或治疗。金雀异黄素已被发现可以降低胰腺癌的患病率。然而，染料木素对胰腺癌细胞的作用分子机制尚未完全阐明。因此，本研究的目的是确认染料木黄酮的抗肿瘤机制。

方法︰ 采用多种分子技术，如实时 RT-PCR、 免疫印迹分析、 入侵检测、 免疫荧光法检测、 基因转染、 MTT检测和组蛋白/ DNA 酶联免疫吸附试验。

结果︰ 我们发现金雀异黄素抑制细胞生长，伴随着FoxM1 和其下游基因比如生存素、 cdc25a、 基质金属蛋白酶-9 和 VEGF诱导的细胞凋亡，抑制胰腺癌细胞的浸润。我们还发现，在金雀异黄素治疗以前用siRNA下调 FoxM1 会导致增强的细胞生长抑制并且诱导细胞凋亡。