Abstract:
Lymphoma and leukemia are both hematological system tumors with complex etiology, and mainly treated with chemotherapeutic drugs. However, therapeutic drugs can interrupt curative effect due to different side effects. Therefore, it is worthwhile to develop a novel therapeutic for providing insights for clinical tumor treatment. In this study, we developed a fisetin nanoparticles (Fisetin NPs) through a self-assembled method, and investigated the activity and potential mechanism of Fisetin NPs against lymphoma and leukemia. The spherical and uniformly distributed Fisetin NPs effectively inhibited both tumor cells proliferation, arrested EL4 cells G0/G1 phase and K562 cells G2/M phase, and induced apoptosis in vitro. In vivo, Fisetin NPs exhibited excellent tumor growth inhibition, effective inhibition of cell proliferation and angiogenesis, significant induction of apoptosis and ideal safety. Mechanically, fisetin upregulated genes (Fas, Pidd, Puma, Apaf1, and p21) in the p53 signaling pathway and bound to N-acetyltransferase 10 (NAT10), ribosomal protein L34 (RPL34) and GTP binding protein 4 (GTPBP4). Collectively, Fisetin NPs have promising therapeutic effects on lymphoma and leukemia, which are of great significant for clinical implications.
摘要:
淋巴瘤和白血病都是血液系统肿瘤,病因复杂,主要用化疗药物治疗。然而,治疗药物会因副作用不同而中断疗效。因此,值得开发一种新的治疗方法,为临床肿瘤治疗提供见解。在这项研究中,我们通过自组装方法开发了一种非塞素纳米粒子(FisetinNPs),并研究了非塞酮NPs抗淋巴瘤和白血病的活性和潜在机制。球形和均匀分布的FisetinNP有效抑制两种肿瘤细胞的增殖,抑制EL4细胞G0/G1期和K562细胞G2/M期,并在体外诱导细胞凋亡。在体内,FisetinNPs表现出优异的肿瘤生长抑制,有效抑制细胞增殖和血管生成,显著诱导细胞凋亡,安全性理想。机械上,非塞素上调基因(Fas,皮德,美洲狮,Apaf1和p21)在p53信号通路中并与N-乙酰转移酶10(NAT10)结合,核糖体蛋白L34(RPL34)和GTP结合蛋白4(GTPBP4)。总的来说,FisetinNPs对淋巴瘤和白血病有很好的治疗效果,这对临床意义非常重要。