2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice.
2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione inhibits the growth and metastasis of breast carcinoma in mice.
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2-十二烷基-6-甲氧基环己-2,5-二烯-1,4-二酮抑制小鼠乳腺癌生长和转移
DOI：
10.1038/s41598-017-07162-3
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发表时间：
2017-07-27
影响因子：
4.6
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Chen C;Nong Z;Xie Q;He J;Cai W;Tang X;Chen X;Huang R;Gao Y
转移导致约90%的女性乳腺癌相关死亡。以前，我们已经证明，2-十二烷基-6-甲氧基环己-2，5-二烯-1，4-二酮（DMDD）显着抑制人乳腺癌细胞的生长，几乎没有毒性。在这项研究中，我们研究了DMDD的毒性和疗效，以治疗转移性乳腺肿瘤的体内小鼠模型的4 T1乳腺癌。DMDD没有引起明显的毒性，并显着延长4 T1荷瘤小鼠的生存期。DMDD在体外能有效抑制4 T1细胞的生长，在体内能有效抑制乳腺肿瘤的生长和转移。DMDD可下调血清中TNF-α、IL-6、IL-12、TGF-β和VEGF的水平。免疫组化结果显示，Bax、caspase-3和caspase-9的激活，Bcl-2、MMP-2和MMP-9、NF-κB和IκBα的表达下调，抑制了肿瘤的生长和转移。我们推测DMDD抑制了小鼠肿瘤细胞中细胞因子的产生，导致NF-κB通路失活，从而抑制了Bcl-2和MMPs等多种抗凋亡和促转移基因的表达。总的来说，我们的研究结果表明，DMDD作为一种安全有效的抗肿瘤药物治疗晚期乳腺癌的潜力。
Metastasis causes approximately 90% of breast cancer-related deaths in women. Previously, we have demonstrated that 2-dodecyl-6-methoxycyclohexa-2,5-diene- 1,4-dione (DMDD) remarkably inhibited the growth of human breast cancer cells with little toxicity. In this study, we investigated the toxicity and efficacy of DMDD to treat metastatic breast tumors using an in vivo mouse model of the 4T1 mammary carcinoma. DMDD caused no observable toxicity and significantly extended the survival of 4T1 tumor-bearing mice. DMDD effectively inhibited the growth of 4T1 cells in vitro, and suppressed the growth and metastasis of mammary tumor in vivo. The levels of inflammatory cytokines in the serum (TNF-α, IL-6, IL-12, TGF-β, and VEGF) were down regulated by DMDD. Immunohistochemical analysis demonstrated that the inhibition of tumor growth and metastasis was associated with activation of Bax, cleaved caspases-3 and -9, and down-regulation of Bcl-2, MMP-2 and -9, NF-κB and IκBα. We speculate that DMDD inhibits cytokine production in the tumor cells in mice, which leads to deactivation of NF-κB pathway, and consequently inhibits the expression of many anti-apoptosis and metastasis-promoting genes, such as Bcl-2 and MMPs. Collectively, our results demonstrate the potential of DMDD as a safe and effective antitumor agent in the treatment of late-stage breast cancer.
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11
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通讯作者：
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作者：
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