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乳腺癌转移是绝大多数乳腺癌患者死亡的原因,而肿瘤干性与转移密切相关.之前研究显示可以通过激动多巴胺D1受体(dopamine D1 receptor,D1DR)来减少肿瘤干细胞(cancer stem-like cells,CSCs).本研究旨在探索新化合物QAP21在转移性乳腺癌细胞中的药效及潜在机制.结果表明,QAP21剂量依赖性地抑制了4T1和MDA-MB-231细胞的集落形成、细胞迁移和侵袭;还明显地抑制了细胞球形成并降低了细胞中CSC比例,说明其较好地抑制了肿瘤干性.QAP21还影响了与肿瘤转移密切相关的NF-κB/Akt/EMT通路的重要分子.此外,QAP21上调了两种细胞的D1DR表达并升高其cAMP和cGMP含量,且D1DR特异性拮抗剂SCH 23390部分或完全拮抗了QAP21的上述作用,均提示QAP21的效应与激动D1DR有关.总之,QAP21有效地降低了转移性乳腺癌细胞的干性和运动能力,提示其可能用于转移性乳腺癌治疗的潜力.“,”Breast cancer is the second leading cause of cancer death in women mainly due to metastasis,which is closely related to cancer stemness.Evidence has shown that cancer stem-like cells(CSCs),which are responsible for cancer stemness,can be decreased by activating dopamine D1 receptor(D1DR).In the present study,we aimed to explore the pharmacological effects as well as the underlying mechanisms of QAP21,a newly synthesized compound that can be orally administered,in metastatic breast cancer cells.Our results showed that QAP21 dose-dependently inhibited the ability of colony formation in 4T1 and MDA-MB-231 cells.Cell mobility,including cell migration and invasion,was also remarkably inhibited.Besides,QAP21 significantly inhibited mammosphere formation and decreased CSC proportion,indicating reduced cancer stemness.We further verified that the nuclear factor-kappa B(NF-κB)/Akt/epithelial-mesenchymal transition(EMT)pathway was markedly impacted by QAP21 treatment.Moreover,QAP21 up-regulated the expressions of D1DR and its second messengers,including cAMP and cGMP,which can be increased when D1DR is activated.SCH 23390,a specific D1DR antagonist,partially or completely reversed the above-mentioned effects of QAP21,indicating that D1DR activation might be involved in the underlying mechanism of QAP21.In summary,QAP21 effectively reduced breast cancer stemness and cell mobility,indicating its potential use for metastatic breast cancer therapy.