Donia Marco, Mijatovic Sanja, Maksimovic-Ivanic Danijela, Miljkovic Djordje, Mangano Katia, Tumino Salvatore, Biondi Antonio, Basile Francesco, Al-Abed Yousef, Stosic-Grujicic Stanislava, Nicoletti Ferdinando
Department of Biomedical Sciences, University of Catania, Italy.
Eur J Pharmacol. 2009 Aug 1;615(1-3):228-33. doi: 10.1016/j.ejphar.2009.04.069. Epub 2009 May 14.
We investigated the effects of the recently synthetized NO donating agent GIT-27NO on the growth of human androgen independent and androgen dependent PC3 and LnCap cells xenografted in nude mice. We also tested the effects of GIT-27NO in the preclinical model of cell-mediated immunoinflammatory hepatitis that can be induced in mice by Concanavalin A (ConA) and that has been shown to benefit from the treatment with NO donating agents such as NO-aspirin. In agreement with in vitro data showing dose-dependent reduction of PC3 and LnCap cell viability with GIT-27NO, the i.p. treatment of mice xenografted with either of these cells with GIT-27NO significantly inhibited their growth as compared to the mice-treated with its vehicle. In addition, GIT-27NO given -24 and -1 h prior to e.v. challenge with 20 mg/kg ConA significantly suppressed the increase of transaminases that occurred 8 h after challenge in the control mice that received the vehicle. In addition, relative to these latter groups of mice, the histological signs of inflammatory hepatitis were markedly reduced in ConA-challenged mice that received GIT-27NO. In the hepatitis model, GIT-27NO was equally effective in preventing ConA-induced hepatitis regardless of whether it was administered intra peritoneally or per os. These data confirm that GIT-27NO is a powerful anticancer agent also endowed with pharmacological properties to prevent the development of cell-mediated murine immunoinflammatory hepatitis.
我们研究了最近合成的一氧化氮供体药物GIT-27NO对裸鼠体内移植的人雄激素非依赖性和雄激素依赖性PC3和LnCap细胞生长的影响。我们还在细胞介导的免疫炎性肝炎的临床前模型中测试了GIT-27NO的作用，该模型可由刀豆蛋白A（ConA）在小鼠中诱导产生，并且已证明使用一氧化氮供体药物（如NO-阿司匹林）进行治疗有益。与体外数据显示GIT-27NO可剂量依赖性降低PC3和LnCap细胞活力一致，用GIT-27NO腹腔注射处理移植了这些细胞之一的小鼠，与用其赋形剂处理的小鼠相比，显著抑制了它们的生长。此外，在静脉注射20 mg/kg ConA前24小时和1小时给予GIT-27NO，可显著抑制在接受赋形剂的对照小鼠中注射后8小时出现的转氨酶升高。此外，相对于后一组小鼠，接受GIT-27NO的ConA攻击小鼠的炎性肝炎组织学迹象明显减轻。在肝炎模型中，无论GIT-27NO是通过腹腔注射还是口服给药，其在预防ConA诱导的肝炎方面同样有效。这些数据证实，GIT-27NO是一种强大的抗癌药物，还具有预防细胞介导的小鼠免疫炎性肝炎发展的药理特性。
