Ma Lingdi, Zhu Zhichao, Jiang Lijia, Sun Xiao, Lu Xuzhang, Zhou Min, Qian Sixuan, Jianyong Li
a Laboratory Center, Changzhou No. 2 People's Hospital, Affiliated Hospital of Nanjing Medical University , Changzhou , China.
b Department of Hematology , Changzhou No. 2 People's Hospital, Affiliated Hospital of Nanjing Medical University , Changzhou , China.
Leuk Lymphoma. 2015;56(10):2923-30. doi: 10.3109/10428194.2015.1007507. Epub 2015 Mar 11.
Matrine, alkaloid isolated from Sophora flavescens, is known to be pleiotropic by exerting anti-inflammatory, anti-oxidation, as well as anti-cancer effects. However, the precise molecular targets or pathways responsible for its activities still remain unclear. The present study aimed to determine the underlying mechanisms of matrine in inhibiting the chronic myeloid leukemia cells (CML). It was observed that matrine treatment significantly suppressed CML cells proliferation, induced apoptosis and resulted in the accumulation of cells in the G0/G1 phase, accompanied by a significant decrease in Bcl-xL, Cyclin D1, and c-Myc expression. Western blot analyses revealed that matrine treatment resulted in the down-regulation in phospho-STAT3 and phospho-JAK2 without significantly effects on STAT3 and JAK2 protein levels. Matrine significantly reduced the expression of IL-6, a potent upstream activating factor of STAT3. These results strongly suggested the IL-6/JAK/STAT3 pathway play an important role in matrine's anti-leukemia effects in K562 cells.
苦参碱是从苦参中分离出的一种生物碱，已知它具有多效性，可发挥抗炎、抗氧化以及抗癌作用。然而，其发挥这些活性作用的确切分子靶点或途径仍不清楚。本研究旨在确定苦参碱抑制慢性髓性白血病细胞（CML）的潜在机制。观察到苦参碱处理显著抑制CML细胞增殖，诱导细胞凋亡，并导致细胞在G0/G1期积累，同时Bcl-xL、细胞周期蛋白D1和c-Myc表达显著降低。蛋白质印迹分析显示，苦参碱处理导致磷酸化STAT3和磷酸化JAK2表达下调，但对STAT3和JAK2蛋白水平无显著影响。苦参碱显著降低了IL-6的表达，IL-6是STAT3的一种有效的上游激活因子。这些结果强烈表明IL-6/JAK/STAT3途径在苦参碱对K562细胞的抗白血病作用中起重要作用。
