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首页> 外文期刊>Drug Design, Development and Therapy >Anti-Breast Cancer Effect of 2-Dodecyl-6-Methoxycyclohexa-2,5-Diene-1,4-Dione in vivo and in vitro Through MAPK Signaling Pathway
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Anti-Breast Cancer Effect of 2-Dodecyl-6-Methoxycyclohexa-2,5-Diene-1,4-Dione in vivo and in vitro Through MAPK Signaling Pathway

机译：通过MAPK信号通路体内和体外抗乳腺癌作用2-十二烷基-6-甲氧基己醇-2,5-二烯-1,4-二酮

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Background: 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) has been reported to inhibit a variety of cancer cell lines. The purpose of this study was to investigate the effects of DMDD on 4T1 breast cancer cells and the effects of DMDD on 4T1 breast cancer in mice and its molecular mechanisms. Methods: 4T1 breast cancer cells were treated with different concentrations of DMDD, and their proliferation, apoptosis, cell-cycle distribution, migration, and invasion were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT, Acridine orange and ethidium bromide dual staining analysis (AO/EB) dual staining, flow cytometry, scratch test, and the Transwell assay. Relative quantitative real-time qPCR analysis and Western blot were applied to examine the expression levels of related genes and proteins. In animal experiments, we established a xenograft model to assess the anti-breast cancer effects of DMDD by evaluating the inhibition rate. The apoptotic activity of DMDD was evaluated by hematoxylin-eosin (HE) staining, transmission electron microscope (TEM) analysis and TdT-mediated dUTP nick end labeling (TUNEL) assays. The mRNA expression levels of MAPK pathway components were detected by relative quantitative real-time qPCR. In addition, the protein expression levels of MAPK pathway components were assessed through immunohistochemical assays and Western blotting. Results: Experiments showed that DMDD could inhibit the proliferation, migration, invasion of 4T1 cells and induce cellular apoptosis and G1 cell cycle arrest. Moreover, DMDD down-regulated the mRNA expressions of raf1, mek1, mek2, erk1, erk2, bcl2, and up-regulated the mRNA expression of bax. DMDD reduced the protein expressions of p-raf1, p-mek, p-erk, p-p38, Bcl2, MMP2, MMP9 and increased the protein expressions of Bax and p-JNK. The results showed that DMDD can effectively reduce the tumor volume and weight of breast cancer in vivo, up-regulate the expression of IL-2, down-regulate the expression of IL-4 and IL-10, induce the apoptosis of breast cancer cells in mice, and regulate the expression of genes and proteins of the MAPK pathway. Conclusion: Our study indicates that DMDD can inhibit proliferation, migration, and invasion and induces apoptosis and cell-cycle arrest of 4T1 breast cancer cells. Also, our findings indicate that DMDD induces the apoptosis of breast cancer cells and inhibits the growth in mice. Its mechanism may be related to the MAPK pathway.
机译：背景：据报道，2-十二烷基-6-甲氧基环己己酸-2,5-二烯-1,4-二酮（DMDD）抑制各种癌细胞系。本研究的目的是探讨DMDD对4T1乳腺癌细胞的影响以及DMDD对小鼠4T1乳腺癌的影响及其分子机制。方法：用不同浓度的DMDD处理4T1乳腺癌细胞，并通过3-（4,5-二甲基-2-噻唑基）-2,5-检测其增殖，细胞凋亡，细胞循环分布，迁移和侵袭。二苯基-2-高唑溴铵（MTT，吖啶橙和溴化乙锭双染色分析（AO / EB）双染色，流式细胞术，划痕试验和Transwell测定。相对定量的实时QPCR分析和Western印迹检查相关基因和蛋白质的表达水平。在动物实验中，我们建立了一种异种移植模型，通过评估抑制率来评估DMDD的抗乳腺癌作用。DMDD的凋亡活性由苏木精 - 曙红（HE）评价DMDD染色，透射电子显微镜（TEM）分析和TDT介导的DUTP缺口末端标记（TUNEL）测定。通过相对定量的实时QPCR检测MAPK途径组分的mRNA表达水平。此外，蛋白质expr通过免疫组织化学测定和蛋白质印迹评估Sapk途径组分的ossion的Mapk途径。结果：实验表明，DMDD可抑制4T1细胞的增殖，迁移，侵袭，并诱导细胞凋亡和G1细胞周期骤停。此外，DMDD下调RAF1，MEK1，MEK2，ERK1，ERK2，BCL2的mRNA表达，并上调BAX的mRNA表达。 DMDD降低了P-RAF1，P-MEK，P-ERK，P-P38，BCL2，MMP2，MMP9的蛋白质表达，并增加了BAX和P-JNK的蛋白质表达。结果表明，DMDD可以有效地降低体内乳腺癌的肿瘤体积和重量，上调IL-2的表达，降低IL-4和IL-10的表达，诱导乳腺癌细胞的凋亡在小鼠中，并调节MAPK途径基因和蛋白质的表达。结论：我们的研究表明，DMDD可以抑制增殖，迁移和侵袭，并诱导4T1乳腺癌细胞的细胞凋亡和细胞周期骤停。此外，我们的研究结果表明DMDD诱导乳腺癌细胞的凋亡并抑制小鼠的生长。其机制可能与MAPK途径有关。

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