Combination of p53 and Rb in the local nano-therapy for rabbit VX2 model of hepatic metastasis carcinoma: the curative effect and safety evaluation

Abstract

Objective Combination of nanoparticle with p53 and Rb gene therapy by gene targeting was applied to investigate its curative effect and safety evaluation on colorectal rabbit hepatic VX2 metastasis for tumor eradication and survival enhancement. Methods Recombinant expressing plasmids harboring wild type p53 and Rb were cotransferred or transferred separately to the rabbit hepatic VX2 metastasis by the emulsion of PLL-nHAP nanoplex and lipodiol through the hepatic artery in a tumor target manner. Subsequent co-expressions of p53 and Rb protein within the treated tumors were detected by Western blot and in situ analysis of confocal laser scanning microscope. The therapeutic effect was evaluated by the tumor growth velocity and the survival time of animals. Eventually, investigations of liver function were applied to evaluate the safety of the process. Results With safe procedure for the rabbits liver function, both p53 and Rb local nano-therapy showed favorable anti-tumor effects and increased animal survival time. p53+ Rb local nano-therapy could significantly inhibit hepatic VX2 metastasis and enhance the animal survival time compared with p53 local nano-therapy or Rb local nano-therapy. Local nano-therapy showed no significant influence to animal liver function. Conclusions Rb can work synergistically with p53 in the combined therapy mediated by PLL-nHAP nanoplex to augment the anti-tumor effect. The local nano-therapy with p53 and Rb is likely to be an effective and safe anti-tumor therapy for hepatic colorectal metastasis. Key words: Nanoparticles; Transfection; Neoplasm hepatic metastasis; Rabbits