Oxytocin effects on the inhibition of the NF-κB/miR195 pathway in mice breast cancer
Oxytocin effects on the inhibition of the NF-κB/miR195 pathway in mice breast cancer
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DOI：
10.1016/j.peptides.2018.07.007
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发表时间：
2018-09-01
期刊：
影响因子：
3
通讯作者：
Khodayari, Hamid
中科院分区：
文献类型：
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作者：
Khori, Vahid;Alizadeh, Ali Mohammad;Khodayari, Hamid
催产素（Oxytocin，OT）对乳腺肿瘤的形成和发展具有抑制作用。推测OT通过抑制NF-κ B B诱导miR-195表达上调，从而促进细胞凋亡，抑制细胞增殖。将32只BALB/c雌性小鼠等分为4组，研究催产素（OT）和催产素受体拮抗剂阿托西班（ATO）对乳腺肿瘤生长的影响。测量动物体重、血浆OT浓度、肿瘤重量和体积。此外，在研究结束时，通过qPCR测定评估肿瘤相关信号传导途径，包括NF-κ B、miR-195和细胞周期蛋白D1，并通过蛋白质印迹评估Akt和ERK蛋白。肿瘤体积和重量在OT给药后显著减小。OT组磷酸化Akt和ERK的表达较肿瘤组明显降低。OT组去磷酸化Akt和ERK的表达较肿瘤组明显增加。与肿瘤组相比，OT组miR-195、OTR和Bax基因的mRNA表达显著升高，ER α、PI 3 K、NF-κ B、cyclin D1和Bcl-2基因的mRNA表达显著降低。有趣的是，ATO给药逆转了这些作用。这些结果可以显示OT在下调NF-κ B和上调miR-195上的新的治疗潜力，并因此在乳腺癌小鼠模型中减少肿瘤体积和重量。
Oxytocin (OT) has the suppressive effects on breast tumor formation and development. We hypothesized that OT through the NF-kappa B inhibition can induce the miR-195 up-regulation which it can promote the cell apoptosis and inhibit the cell proliferation. Thirty-two BALB/c female mice were equally divided into four groups to study the effects of OT and atosiban (ATO) (an oxytocin receptor antagonist) on the mammary tumor growth. The animal weight, OT plasma concentration, and the tumor weight and volume were measured. Moreover, the tumor-related signaling pathways including NF-kappa B, miR-195, and Cyclin Dl were evaluated by qPCR assays, and Akt and ERK proteins were assessed by western blot at the end of the study. The volume and weight of tumors were significantly decreased after OT administration. The phosphorylated Akt and ERK expressions were significantly decreased in the OT group compared to the tumor group. In contrast, the dephosphorylated Akt and ERK expressions were significantly increased in the OT group in comparison with the tumor group. The mRNA expressions of miR-195, OTR, and Bax genes were significantly increased, and the mRNA expression of ER alpha, PI3K, NF-kappa B, cyclin Dl and Bcl-2 genes were decreased in the OT group in comparison with the tumor group. Interestingly, ATO administration reversed these effects. These results can exhibit a new therapeutic potential for OT on the down-regulation of the NF-kappa B and up-regulation of miR-195 and consequently, decrease of the tumor volume and weight in a mouse model of breast cancer.