FoxM1 is a novel target of a natural agent in pancreatic cancer.
FoxM1 is a novel target of a natural agent in pancreatic cancer.
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DOI：
10.1007/s11095-010-0106-x
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发表时间：
2010-06
影响因子：
3.7
通讯作者：
Sarkar, Fazlul H.
中科院分区：
文献类型：
--
作者：
Wang, Zhiwei;Ahmad, Aamir;Banerjee, Sanjeev;Azmi, Asfar;Kong, Dejuan;Li, Yiwei;Sarkar, Fazlul H.
胰腺癌仍然是美国癌症相关死亡的第四大常见原因。因此，迫切需要新的预防和/或治疗策略。已发现染料木黄酮是降低胰腺癌发病率的原因。然而，染料木黄酮发挥其对胰腺癌细胞作用的分子机制尚未完全阐明。因此，本研究的目的是阐明染料木黄酮的抗癌机制。采用Real-time RT-PCR、Western blot、侵袭实验、免疫荧光实验、基因转染、MTT实验、组蛋白/DNA ELISA等多种分子生物学技术。我们发现，染料木黄酮抑制细胞生长伴随着诱导凋亡与随之衰减FoxM 1及其下游基因，如生存素，cdc 25 a，MMP-9，和VEGF，从而抑制胰腺癌细胞的侵袭。我们还发现，下调FoxM 1的siRNA前金雀异黄素治疗导致增强细胞生长抑制和诱导凋亡。这是第一份显示FoxM 1在介导染料木黄酮在胰腺癌细胞中的生物学效应中的分子作用的报告，表明FoxM 1可能是治疗胰腺癌的新靶点。
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. 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. 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. 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.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
3.8
作者：
Bektas, Nuran;ten Haaf, Anette;Veeck, Juergen;Wild, Peter Johannes;Luescher-Firzlaff, Juliane;Hartmann, Arndt;Knuechel, Ruth;Dahl, Edgar
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11.4
作者：
Park, Hyun Jung;Carr, Janai R.;Raychaudhuri, Pradip
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Raychaudhuri, Pradip
影响因子：
3.7
作者：
Gemenetzidis E;Bose A;Riaz AM;Chaplin T;Young BD;Ali M;Sugden D;Thurlow JK;Cheong SC;Teo SH;Wan H;Waseem A;Parkinson EK;Fortune F;Teh MT
通讯作者：
Teh MT
影响因子：
5.2
作者：
Francis RE;Myatt SS;Krol J;Hartman J;Peck B;McGovern UB;Wang J;Guest SK;Filipovic A;Gojis O;Palmieri C;Peston D;Shousha S;Yu Q;Sicinski P;Coombes RC;Lam EW
通讯作者：
Lam EW