Synthetic triterpenoid CDDO prevents the progression and metastasis of prostate cancer in TRAMP mice by inhibiting survival signaling
Synthetic triterpenoid CDDO prevents the progression and metastasis of prostate cancer in TRAMP mice by inhibiting survival signaling
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DOI：
10.1093/carcin/bgr030
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发表时间：
2011-05-01
期刊：
影响因子：
4.7
通讯作者：
Gautam, Subhash C.
中科院分区：
文献类型：
--
作者：
Deeb, Dorrah;Gao, Xiaohua;Gautam, Subhash C.
在我们之前研究的扩展中，显示了合成的齐墩果酸三萜类化合物对前列腺癌细胞系的有效抗肿瘤活性，我们检查了2-氰基-3，12-二氧代齐墩果酸-1，9（11）-二烯-28-酸（CDDO）在预防小鼠前列腺转基因腺癌（TRAMP）模型中前列腺癌的发展和/或进展方面的功效。数据显示，用CDDO（10 μ mol/kg）经口管饲20周导致抑制背外侧前列腺和腹侧前列腺中的癌前病变向腺癌的进展，而没有毒性。CDDO还能抑制肿瘤向远处器官的转移。用CDDO处理显著抑制前列腺组织中的细胞增殖，减少血管密度，并促进凋亡。此外，Akt、NF-κ B和NF-κ B调节的Bcl-2、Bcl-xL、存活素和cIAP 1似乎是CDDO抑制TRAMP小鼠中前列腺癌进展的分子靶标。因此，这些研究首次显示了CDDO化学预防人前列腺癌的潜力。
In an extension of our previous studies showing potent antitumorigenic activity of synthetic triterpenoids of oleanolic acid against prostate cancer cell lines, we examined the efficacy of 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) in preventing the development and/or progression of prostate cancer in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Data show that oral gavage with CDDO (10 mu mol/kg) for 20 weeks resulted in inhibition of the progression of preneoplastic lesions in the dorsolateral prostate and ventral prostate to adenocarcinoma without toxicity. CDDO also inhibited metastasis of tumor to the distant organs. Treatment with CDDO significantly inhibited cell proliferation, reduced the density of blood vessels and promoted apoptosis in the prostatic tissue. Further, Akt, NF-kappa B and NF-kappa B regulated Bcl-2, Bcl-xL, survivin and cIAP1 appear to be the molecular targets of CDDO for inhibiting the progression of prostate cancer in TRAMP mice. Thus, these studies show for the first time the potential of CDDO for chemoprevention of human prostate cancer.