A thiosemicarbazone derivative induces triple negative breast cancer cell apoptosis: possible role of miRNA-125a-5p and miRNA-181a-5p
作者:Rania El Majzoub、Mohammad Fayyad-kazan、Assaad Nasr El Dine、Rawan Makki、Eva Hamade、René Grée、Ali Hachem、Rabih Talhouk、Hussein Fayyad-Kazan、Bassam Badran
DOI:10.1007/s13258-019-00866-y
日期:2019.12
BACKGROUND Breast cancer, the most commonly diagnosed malignancy in women, accounts for the highest cancer-related deaths worldwide. Triple negative breast cancer (TNBC), lacking the expression of estrogen, progesterone and HER2 receptors, has an aggressive clinical phenotype and is susceptible to chemotherapy but not to hormonal or targeted immunotherapy. In an attempt to identify potent and selective
背景技术乳腺癌是女性中最常被诊断出的恶性肿瘤,在全球范围内与癌症相关的死亡人数最高。三阴性乳腺癌(TNBC)缺乏雌激素,孕激素和HER2受体的表达,具有侵略性的临床表型,易受化学疗法的影响,但对激素或靶向免疫疗法不敏感。为了鉴定有效和选择性的抗TNBC剂,针对硫代半碳酰胺衍生物对MDA-MB 231乳腺癌细胞系的细胞毒活性进行了筛选。方法采用MTT法检测细胞活力。通过蛋白质印迹评估P53磷酸化状态,聚(ADP-核糖)聚合酶(PARP)裂解以及Bcl2和Bax蛋白水平。进行实时定量PCR以表征miRNA的表达水平。结果顺铂+硫半脲化合物4的组合显示出有效的抗TNBC潜力。顺铂+化合物4显着增强了TNBC中的p53磷酸化,诱导的Bax量,降低的Bcl2蛋白水平,增强的PARP裂解和调节的miRNA表达谱,特别是miR-125a-5p和miR-181a-5p的过表达。有趣的是,miR-125a-