Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran.
Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Biol Res. 2019 Aug 6;52(1):40. doi: 10.1186/s40659-019-0247-2.
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.
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.
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.
This study highlights an anti-metastatic role for a novel hydrazide derivative in both in vitro and in vivo models of breast cancer.
目前有许多阻碍乳腺癌成功治疗的障碍，包括癌细胞的转移扩散。在寻找新的抗癌药物时，我们报道了两种具有人类乳腺癌细胞抗癌活性的新型酰腙衍生物。本研究旨在探索最有效的一种，N'-((5-硝基噻吩-2-基)亚甲基)-2-(苯硫基)苯甲酰肼（化合物 B），对转移性乳腺癌的治疗潜力，转移性乳腺癌对现有化疗药物有耐药性。
将 4T1 乳腺癌细胞接种于 5-7 周龄雌性 BALB/c 小鼠的脂肪垫乳腺中，然后腹腔内给予有效化合物 4 周。用免疫组织化学法检测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 细胞侵袭的影响。
我们的结果表明，这种有效的衍生物显著抑制了 MDA-MB-231 细胞在体外的侵袭，如 Matrigel 测定和 MMP-9 表达的定量实时方法所示，在 48 小时的治疗后。在剂量为 1mg/kg 的情况下，每日给予该化合物可抑制原发性肿瘤及其向肺部的转移，这在 4T1 乳腺癌的同源 BALB/c 小鼠的著名转移模型中得到了证实。肿瘤和肺组织的免疫组织化学检查支持了这些结果。与对照组相比，用有效化合物治疗的小鼠的肿瘤和肺部显示出增殖指数降低和微血管密度减小。
本研究强调了一种新型酰腙衍生物在乳腺癌的体外和体内模型中具有抗转移作用。
