Department of Nutrition, University of California, Davis, One Shields Ave, Davis, CA, 95616, USA.
Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, NY, 11794-8175, USA.
Arch Biochem Biophys. 2018 Jun 15;648:12-19. doi: 10.1016/j.abb.2018.04.012. Epub 2018 Apr 18.
Curcumin reduces Hodgkin's lymphoma (HL) cell growth in vitro, but its unfavorable pharmacokinetics highlight the need for novel in vivo delivery systems. Thus, we explored whether formulation of curcumin in solid lipid nanoparticles (SLN-curc) or d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (TPGS-curc) could enhance its efficacy in mice. Curcumin formulated in SLN and in TPGS resulted in higher curcumin plasma levels in mice. Compared to vehicle-treated controls, SLN-curc and TPGS-curc reduced HL xenograft growth by 50.5% (p < 0.02) and 43.0% (p < 0.04), respectively, while curcumin reduced it by 35.8% (p < 0.05). In addition, SLN-curc reduced the expression of proteins involved in cell proliferation and apoptosis (XIAP and Mcl-1) in HL tumor extracts. In HL cells in culture, curcumin decreased the expression of relevant anti-inflammatory cytokines (IL-6 and TNF-α) in a concentration-dependent manner. Moreover, when given in combination with bleomycin, doxorubicin and vinblastine, curcumin showed an additive growth inhibitory effect. In conclusion, SLNs appear as an appropriate and effective drug delivery system for curcumin. Given the efficacy of SLN-curc and the enhanced growth inhibitory effect when combined with chemotherapeutic drugs, we speculate that curcumin, when appropriately formulated, is a promising adjuvant agent for the treatment of HL and merits further evaluation.
姜黄素可减少体外霍奇金淋巴瘤（HL）细胞的生长，但由于其不利的药代动力学特性，因此需要开发新的体内给药系统。因此，我们探索了姜黄素是否可以被制成固体脂质纳米粒（SLN-curc）或维生素 E 聚乙二醇 1000 琥珀酸酯（TPGS）纳米粒（TPGS-curc）以增强其在小鼠体内的疗效。在 SLN 和 TPGS 中制成的姜黄素可使小鼠体内的姜黄素血浆水平升高。与载体处理的对照组相比，SLN-curc 和 TPGS-curc 分别使 HL 异种移植物的生长减少了 50.5%（p<0.02）和 43.0%（p<0.04），而姜黄素使生长减少了 35.8%（p<0.05）。此外，SLN-curc 降低了 HL 肿瘤提取物中与细胞增殖和凋亡相关的蛋白（XIAP 和 Mcl-1）的表达。在培养的 HL 细胞中，姜黄素呈浓度依赖性降低了相关抗炎细胞因子（IL-6 和 TNF-α）的表达。此外，当与博来霉素、阿霉素和长春碱联合使用时，姜黄素显示出相加的生长抑制作用。总之，SLN 似乎是姜黄素的一种合适且有效的药物递送系统。鉴于 SLN-curc 的疗效以及与化疗药物联合使用时增强的生长抑制作用，我们推测姜黄素在适当的配方下，是治疗 HL 的一种很有前途的辅助药物，值得进一步评估。
