Kim Minhyung, Blum Asher B, Haslinger Michelle L, Donahue Michael J, Fisher Daniel T, Skitzki Joseph J, Park Il Young
Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA,
Surg Today. 2015 Mar;45(3):355-62. doi: 10.1007/s00595-014-0952-y. Epub 2014 Jul 8.
Quinacrine is a relatively non-toxic drug, once given almost exclusively for malaria. However, recent studies show that quinacrine can suppress nuclear factor-κB (NF-κB), and activate p53 signaling. We investigated the anti-cancer effect of quinacrine, using a novel mouse model of isolated limb perfusion (ILP) for extremity melanoma.
Female C57BL/6 mice (22-25 g) were injected with B16 melanoma cells (1 × 10(5)) subcutaneously in the distal thigh. After 7 days of tumor establishment, mice were perfused with either PBS, melphalan (90 µg), or quinacrine (3.5 and 4.5 mg) through the superficial femoral artery for 30 min at either 37 or 42 °C in a non-oxygenated circuit. We analyzed morbidity, toxicity, tumor apoptosis, and responses.
Melanoma cell death following in vitro exposure to quinacrine was dose and time dependent. A significant decrease in mean tumor volume was observed after perfusion with low-dose and high-dose quinacrine (both P = 0.002) at 37 °C as well as after perfusion with low-dose quinacrine (P = 0.0008) at 42 °C.
Quinacrine has demonstrable efficacy against melanoma cells in vitro and in a clinically relevant model of ILP. Further studies to evaluate the optimal conditions for quinacrine usage are warranted.
喹吖因是一种相对无毒的药物，曾经几乎仅用于治疗疟疾。然而，最近的研究表明，喹吖因可抑制核因子κB（NF-κB）并激活p53信号传导。我们使用一种用于肢体黑色素瘤的新型离体肢体灌注（ILP）小鼠模型，研究了喹吖因的抗癌作用。
将雌性C57BL/6小鼠（22 - 25克）的大腿远端皮下注射B16黑色素瘤细胞（1×10⁵）。肿瘤形成7天后，在无氧循环中，于37℃或42℃通过股浅动脉对小鼠灌注磷酸盐缓冲液（PBS）、美法仑（90微克）或喹吖因（3.5毫克和4.5毫克）30分钟。我们分析了发病率、毒性、肿瘤细胞凋亡及反应。
体外暴露于喹吖因后黑色素瘤细胞死亡呈剂量和时间依赖性。在37℃用低剂量和高剂量喹吖因灌注后（均P = 0.002）以及在42℃用低剂量喹吖因灌注后（P = 0.0008），平均肿瘤体积均显著减小。
喹吖因在体外以及在临床相关的ILP模型中对黑色素瘤细胞具有明显疗效。有必要进一步研究以评估喹吖因使用的最佳条件。
