Steel Jason C, Kalle Wouter H J, Dingwall Daniel J, Cavanagh Heather M A, Burton Mark A
School of Biomedical Science, Charles Sturt University, P.O. Box 588, Wagga Wagga 2678, Australia.
Cancer Ther. 2004;2:239-244.
Successful liposomal-mediated gene therapy is often limited by poor transfection efficiencies. One method previously shown to increase the efficiency of liposomal gene delivery is through the administration of a non-therapeutic dose of the chemotherapeutic drug cisplatin prior to lipofection. The currents study aims to utilise this method to deliver lipoplexes containing the p53 tumour suppressor gene with the aim of increasing therapeutic effect of the p53 gene on a solid tumour in vivo. Rats, implanted with solid salivary adenocarcinomas, were pre-treated with a low dose of cisplatin seven days prior to liposomal mediated p53 treatment. Following treatment with p53, tumour growth, p53 expression and levels of apoptosis were examined and compared to animals treated with p53 without cisplatin pre-treatment and a saline control. Tumours that had been pre-treated with cisplatin prior to p53-lipofection were significantly smaller than both the saline control and the non-cisplatin treated tumours. Saline treated tumours increased in size by an average of 164% over a 96-hour period compared to 64% and 101% for the cisplatin and non-cisplatin p53-liposome treated tumours. The cisplatin pre-treated tumours resulted in significantly higher levels of apoptosis surrounding the treatment site and exhibited prolonged p53 expression when compared to the non-cisplatin pre-treated tumours. The results suggest that the use of cisplatin to pre-sensitise tumours to lipofection has significant benefits when used in conjunction with p53.
成功的脂质体介导的基因治疗通常受到转染效率低下的限制。先前显示的一种提高脂质体基因递送效率的方法是在脂质体转染之前给予非治疗剂量的化疗药物顺铂。当前的研究旨在利用这种方法递送含有p53肿瘤抑制基因的脂质复合物，以提高p53基因对体内实体瘤的治疗效果。将植入实体唾液腺癌的大鼠在脂质体介导的p53治疗前7天用低剂量顺铂进行预处理。在用p53治疗后，检查肿瘤生长、p53表达和凋亡水平，并与未进行顺铂预处理而用p53治疗的动物以及生理盐水对照组进行比较。在进行p53-脂质体转染之前用顺铂预处理的肿瘤明显小于生理盐水对照组和未用顺铂治疗的肿瘤。在96小时内，生理盐水处理的肿瘤大小平均增加了164%，而顺铂处理的肿瘤和未用顺铂处理的p53-脂质体处理的肿瘤分别增加了64%和101%。与未用顺铂预处理的肿瘤相比，顺铂预处理的肿瘤在治疗部位周围导致明显更高的凋亡水平，并表现出更长时间的p53表达。结果表明，当与p53联合使用时，使用顺铂使肿瘤对脂质体转染预先致敏具有显著益处。
