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 ca...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(D1 DR).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 4 T1 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 D1 DR and its second messengers,including cAMP and cGMP,which can be increased when D1 DR is activated.SCH 23390,a specific D1 DR antagonist,partially or completely reversed the above-mentioned effects of QAP21,indicating that D1 DR 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.展开更多
基金Beijing Municipal Natural Science Foundation(Grant No.7192100)Innovation Team of Ministry of Education(Grant No.BMU2017TD003)。
文摘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(D1 DR).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 4 T1 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 D1 DR and its second messengers,including cAMP and cGMP,which can be increased when D1 DR is activated.SCH 23390,a specific D1 DR antagonist,partially or completely reversed the above-mentioned effects of QAP21,indicating that D1 DR 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.
文摘本文结合二次分配问题(quadratic assignment problem,QAP)的特点,通过分析传统蚂蚁算法在解决QAP问题时收敛过快,精度不高的缺点,提出一种以ACS(ant colony system)为基础的改进蚁群算法――信息素迭代累积ACS(ACS with accumu-lated pheromone by iteration,ACS_API)。新方法通过对定义启发式信息和信息素更新规则的改进,扩大了搜索空间,从而避免过早收敛,陷入局部最优解中。该算法已应用于QAP标准测试数据,并通过与另外两种先前提出的改进蚂蚁算法(HAS_QAP,ACO_GLS)的比较分析得出了它在算法精度和执行时间上的优势。
