Department of Hematology, Institute of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China; Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
Int J Pharm. 2024 Apr 10;654:123971. doi: 10.1016/j.ijpharm.2024.123971. Epub 2024 Mar 6.
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.
淋巴瘤和白血病均为起源于造血系统的肿瘤，其病因复杂，主要采用化疗药物治疗。然而，由于治疗药物的不同副作用，可能会中断疗效。因此，开发新型治疗方法为临床肿瘤治疗提供思路是非常值得的。在本研究中，我们采用自组装的方法制备了根皮素纳米粒（Fisetin NPs），并研究了 Fisetin NPs 对淋巴瘤和白血病的活性及潜在作用机制。结果显示，球形且分布均匀的 Fisetin NPs 能够有效抑制肿瘤细胞的增殖，将 EL4 细胞阻滞于 G0/G1 期，将 K562 细胞阻滞于 G2/M 期，并诱导细胞发生凋亡。体内实验表明，Fisetin NPs 能够显著抑制肿瘤生长，有效抑制肿瘤细胞增殖和血管生成，显著诱导肿瘤细胞发生凋亡，同时具有理想的安全性。机制研究表明，根皮素能够上调 p53 信号通路中的基因（Fas、Pidd、Puma、Apaf1 和 p21），并与 N-乙酰转移酶 10（NAT10）、核糖体蛋白 L34（RPL34）和 GTP 结合蛋白 4（GTPBP4）结合。综上所述，Fisetin NPs 对淋巴瘤和白血病具有较好的治疗效果，具有重要的临床应用价值。
