Combination of ginsenoside Rg3 with docetaxel enhances the susceptibility of prostate cancer cells via inhibition of NF-κB
Combination of ginsenoside Rg3 with docetaxel enhances the susceptibility of prostate cancer cells via inhibition of NF-κB
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DOI：
10.1016/j.ejphar.2009.12.018
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发表时间：
2010-04-10
影响因子：
5
通讯作者：
Hong, Jin Tae
中科院分区：
文献类型：
--
作者：
Kim, Sun Mi;Lee, So Yong;Hong, Jin Tae
人参皂苷Rg3作为一种癌症预防或治疗药物一直是人们感兴趣的课题。核因子-kappa （NF-kappa B）在前列腺癌中组成性激活，并使癌细胞对化疗药物产生耐药性。为了研究Rg3是否可以抑制NF-kappa B的激活，从而增加前列腺（LNCaP和PC-3、DU145）细胞对化疗药物的易感性，我们检测了前列腺癌细胞的生长和NF-kappa B的激活。我们发现Rg3 （50 μ M）与传统药物多西紫杉醇（5 nM）联合治疗在抑制前列腺癌细胞生长和诱导凋亡以及G(0)/G(1)阻滞并显著抑制NF-kappa B活性方面比Rg3或多西紫杉醇单独治疗更有效。同时发现NF-kappa B靶基因Bax、caspase-3、caspase-9的表达明显增强，但联合处理对Bcl-2、凋亡抑制蛋白（IAP-1）、X染色体IAP （XIAP）的表达以及细胞周期调节蛋白cyclin B、D1、E、cyclin依赖性激酶2、4的表达也明显抑制。Rg3 （50 μ M）联合顺铂（10 μ M）和阿霉素（2 μ M）对前列腺癌细胞生长和nf - κ B活性的抑制也比Rg3或化疗药物单独治疗更有效。说明人参皂苷Rg3可抑制nf - κ B，增强前列腺癌细胞对多西紫杉醇等化疗药物的敏感性。因此，人参皂苷Rg3可能是一种有用的抗癌剂。(C) 2009 Elsevier B.V.版权所有
Ginsenoside Rg3 has been a subject of interest for use as a cancer preventive or therapeutic agent. Nuclear factor-kappa (NF-kappa B) is constitutively activated in prostate cancer, and gives cancer cells resistance to chemotherapeutic agents. To investigate whether Rg3 can suppress the activation of NF-kappa B, and thus increase susceptibility of prostate (LNCaP and PC-3, DU145) cells against chemotherapeutics, prostate cancer cell growth as well as activation of NF-kappa B was examined. We found that a combination treatment of Rg3 (50 mu M) with a conventional agent docetaxel (5 nM) was more effective in the inhibition of prostate cancer cell growth and induction of apoptosis as well as G(0)/G(1) arrest accompanied with the significant inhibition of NF-kappa B activity than those by treatment of Rg3 or docetaxel alone. It was also found that NF-kappa B target gene expression of Bax, caspase-3, and caspase-9 was much more significantly enhanced, but the expression of Bcl-2, inhibitor of apoptosis protein (IAP-1) and X chromosome IAP (XIAP), and the expression of cell cycle regulatory proteins cyclin B, D1 and E, and cyclin dependent kinases 2 and 4 was also much more significantly inhibited by the combination treatment. The combination of Rg3 (50 mu M) with cisplatin (10 mu M) and doxorubicin (2 mu M) was also more effective in the inhibition of prostate cancer cell growth and NF-kappa B activity than those by the treatment of Rg3 or chemotherapeutics alone. These results indicate that ginsenoside Rg3 inhibits NF-kappa B, and enhances the susceptibility of prostate cancer cells to docetaxel and other chemotherapeutics. Thus, ginsenoside Rg3 could be useful as an anti-cancer agent. (C) 2009 Elsevier B.V. All rights reserved.