摘要
三阴性乳腺癌是一种异质性复发性癌症,与转移率高、预后差和缺乏治疗靶点有关,而抑制CDK4/6靶点可产生抗肿瘤作用。设计并合成了一种新型的Abemaciclib衍生物,命名为WXJ-112,探讨了化合物WXJ-112对TNBC生物学等方面的影响。用甲基噻唑四唑法测定细胞活力,通过克隆形成试验、划痕试验和侵袭试验检测克隆形成、迁移和侵袭能力。Western blot分析检测CDK4/6-Rb-E2F通路相关蛋白的表达,在鸡胚移植肿瘤模型中探讨其肿瘤抑制作用。试验结果表明,WXJ-112可抑制MDA-MB-231细胞增殖、集落形成、迁移和侵袭,诱导周期阻滞,并且在鸡胚移植肿瘤模型中具有显著的抗肿瘤活性作用。综上所述,化合物WXJ-112具有良好的抗肿瘤细胞增殖作用,可作为一种很有前途的乳腺癌治疗的候选药物。
Triple-negative breast cancer(TNBC)is a heterogeneous recurrent cancer associated with high metastasis,poor prognosis,and a lack of therapeutic targets,while inhibition of CDK4/6 targets produces anti-tumor effects.In the present study,a novel Abemaciclib derivative named WXJ-112 was designed and synthesized.The effect of compound WXJ-112 on several aspects of TNBC biology was investigated.Cell viability was measured by the methylthiazolium tetrazolium(MTT)assay and clone formation,migration,and invasion ability was detected by clone formation assay,scratch assay,and invasion assay.Western blot analysis was performed to detect the expression of proteins related to the CDK4/6-Rb-E2F pathway.The tumor suppressor effect was investigated in a chicken embryo transplantation tumor model.The experimental results showed that WXJ-112 inhibited the proliferation,colony formation,migration,and invasion of MDA-MB-231 cells,induced cycle blockade,and acted as a significant anti-tumor activity in the chicken embryo transplantation tumor model.In summary,compound WXJ-112 has good anti-tumor cell proliferation effects and can be used as a promising drug candidate for breast cancer treatment.
作者
左玲怡
何景梁
成文浩
张思懿
李寒雪
周娇娇
张美琪
刘媛媛
覃静婷
钱其兰
敬爱新
王秀军
刘彬
ZUO Lingyi;HE Jingliang;CHENG Wenhao;ZHANG Siyi;LI Hanxue;ZHOU Jiaojiao;ZHANG Meiqi;LIU Yuanyuan;QIN Jingting;QIAN Qilan;JING Aixin;WANG Xiujun;LIU Bin(School of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,China;Jiangsu Key Laboratory of Marine Drug Active Molecular Screening,Jiangsu Ocean University,Lianyungang 222005,China)
出处
《江苏海洋大学学报（自然科学版）》
CAS
2024年第4期40-50,共11页
Journal of Jiangsu Ocean University:Natural Science Edition
