Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis.
Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis.
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DOI：
10.1186/1476-4598-7-16
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发表时间：
2008-01-29
期刊：
影响因子：
37.3
通讯作者：
Srivastava RK
中科院分区：
文献类型：
--
作者：
Shankar S;Ganapathy S;Chen Q;Srivastava RK
我们最近已经表明，姜黄素（二阿魏酰甲烷，姜黄中的黄色色素）增强前列腺癌PC-3细胞中TRAIL的凋亡诱导潜力，并通过多种机制在体外使TRAIL抗性LNCaP细胞增敏。本研究的目的是研究姜黄素致敏体内TRAIL抗性LNCaP异种移植物的分子机制。将前列腺癌TRAIL抗性LNCaP细胞植入Balb c裸鼠中以检查姜黄素和/或TRAIL对肿瘤生长和与细胞凋亡、转移和血管生成相关的基因的影响。姜黄素通过诱导凋亡（TUNEL染色）和抑制增殖（PCNA和Ki 67染色）抑制裸鼠LNCaP异种移植瘤的生长，并通过TRAIL使这些肿瘤敏感以经历凋亡。在异种移植瘤中，姜黄素上调TRAIL-R1/DR 4、TRAIL-R2/DR 5、Bax、巴克、p21/WAF 1和p27/KIP 1的表达，抑制NFκB及其基因产物cyclin D1、VEGF、uPA、MMP-2、MMP-9、Bcl-2和Bcl-XL的活化。死亡受体和Bcl-2家族成员的调节以及NFκB的失活可能使TRAIL耐药的LNCaP异种移植物增敏。姜黄素还抑制肿瘤中的血管数量和小鼠中循环内皮生长因子受体2阳性内皮细胞。姜黄素抑制肿瘤生长、转移和血管生成以及增强TRAIL的治疗潜力的能力表明，姜黄素单独或与TRAIL组合可用于前列腺癌预防和/或治疗。
We have recently shown that curcumin (a diferuloylmethane, the yellow pigment in turmeric) enhances apoptosis-inducing potential of TRAIL in prostate cancer PC-3 cells, and sensitizes TRAIL-resistant LNCaP cells in vitro through multiple mechanisms. The objectives of this study were to investigate the molecular mechanisms by which curcumin sensitized TRAIL-resistant LNCaP xenografts in vivo. Prostate cancer TRAIL-resistant LNCaP cells were implanted in Balb c nude mice to examine the effects of curcumin and/or TRAIL on tumor growth and genes related to apoptosis, metastasis and angiogenesis. Curcumin inhibited growth of LNCaP xenografts in nude mice by inducing apoptosis (TUNEL staining) and inhibiting proliferation (PCNA and Ki67 staining), and sensitized these tumors to undergo apoptosis by TRAIL. In xenogrfated tumors, curcumin upregulated the expression of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax, Bak, p21/WAF1, and p27/KIP1, and inhibited the activation of NFκB and its gene products such as cyclin D1, VEGF, uPA, MMP-2, MMP-9, Bcl-2 and Bcl-XL. The regulation of death receptors and members of Bcl-2 family, and inactivation of NFκB may sensitize TRAIL-resistant LNCaP xenografts. Curcumin also inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells in mice. The ability of curcumin to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that curcumin alone or in combination with TRAIL can be used for prostate cancer prevention and/or therapy.
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影响因子：
5.8
作者：
Aggarwal, Bharat B.;Banerjee, Sanjeev;Sethi, Gautam
通讯作者：
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Schwall, RH