BACKGROUND There are currently a number of barriers hindering the successful treatment of breast cancer, including the metastatic spread of cancer cells. In looking for new anticancer agents, we reported two novel hydrazide derivatives with anti-cancer activity in human breast cancer cells. The current study aims to explore the therapeutic potential of the most effective one, N'-((5-nitrothiophen-2-yl)methylene)-2-(phenylthio)benzohydrazide (compound B), on metastatic breast cancer, which is resistant to available chemotherapeutics. METHODS 4T1 mammary carcinoma cells were inoculated into the fat pad mammary of 5-7-week-old female BALB/c mice and then the effective compound was intraperitoneally administered for 4 weeks. Proliferation index and angiogenesis in tumor and lung tissues were examined with immunohistochemistry. In vitro assessments were also carried out to evaluate the effect of the compound on invasion of MDA-MB-231 cells. RESULTS Our results demonstrated that this effective derivative significantly inhibited invasion of MDA-MB-231 cells in vitro as shown by Matrigel assay and quantitative real-time method for MMP-9 expression after 48 h of treatment. Daily administration of the compound suppressed the growth of primary tumor and its metastasis to lung, which was confirmed by H&E experiment at a dose of 1 mg/kg in a well-known metastatic model of 4T1 breast cancer in syngeneic BALB/c mice. These outcomes were supported by the immunohistochemical examinations of the tumor and lung tissues of mice. Tumors and lungs in mice treated with the effective compound showed a reduced proliferation index and a smaller microvessel density compared to the control. CONCLUSION This study highlights an anti-metastatic role for a novel hydrazide derivative in both in vitro and in vivo models of breast cancer.

中文翻译：

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一种新型的酰肼化合物对乳腺癌具有抗转移作用。

背景技术目前存在许多阻碍乳腺癌成功治疗的障碍，包括癌细胞的转移扩散。在寻找新的抗癌剂时，我们报道了两种在人乳腺癌细胞中具有抗癌活性的酰肼衍生物。本研究旨在探讨最有效的一种N'-（（5-硝基噻吩-2-基）亚甲基）-2-（苯硫基）苯并酰肼（化合物B）对转移性乳腺癌的治疗潜力可用的化学疗法。方法将4T1乳腺癌细胞接种到5-7周龄雌性BALB / c小鼠的脂肪垫乳腺中，然后将有效化合物腹膜内给药4周。用免疫组织化学检查肿瘤和肺组织中的增殖指数和血管生成。还进行了体外评估以评估该化合物对MDA-MB-231细胞侵袭的作用。结果我们的结果证明，如治疗48小时后，通过Matrigel分析和定量实时方法检测MMP-9的表达，该有效衍生物可显着抑制MDA-MB-231细胞的体外侵袭。化合物的每日给药抑制了原发性肿瘤的生长及其向肺的转移，这是通过H＆E实验在同系BALB / c小鼠的一种众所周知的4T1乳腺癌转移模型中以1 mg / kg的剂量证实的。这些结果得到了小鼠肿瘤和肺组织免疫组织化学检查的支持。与对照相比，用有效化合物处理的小鼠的肿瘤和肺部显示出较低的增殖指数和较小的微血管密度。结论这项研究强调了一种新型酰肼衍生物在乳腺癌的体内和体外模型中的抗转移作用。