Efficient dose-dependent and time-dependent protein transduction of pancreatic carcinoma cells in vitro and in vivo using purified VP22-EGFP fusion protein

被引:5
作者
Boenicke, L
Chu, K
Pauls, R
Tams, C
Kruse, ML
Kurdow, R
Schniewind, B
Böhle, A
Kremer, B
Kalthoff, H
机构
[1] UKSH, Clin Gen & Thorac Surg, Mol Oncol Res Lab, D-24105 Kiel, Germany
[2] UKSH, Dept Med 1, D-24105 Kiel, Germany
来源
JOURNAL OF MOLECULAR MEDICINE-JMM | 2003年 / 81卷 / 03期
关键词
VP22; protein transduction; fusion protein; nickel resin purification; Xenotransplantation model;
D O I
10.1007/s00109-003-0421-3
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
We constructed a prokaryotic vector expressing a truncated VP22-EGFP gene and purified this fusion protein from Escherichia coli cultures using nickel resin. Application of purified VP22-EGFP protein to human pancreatic carcinoma cells showed a highly efficient time-dependent and dose-dependent uptake and resulted in green fluorescence predominantly located in the nuclei of treated cells. Purified VP22-EGFP efficiently translocated into deeper layers of pancreatic tumor cell spheroids. Homogeneous uptake into the whole tumor was observed after peritumoral injection in human pancreatic tumors in SCID mice. We conclude that the direct application of purified VP22 fusion proteins offers a new, peptide-mediated and potentially systemic therapy for pancreatic cancer. This opens the possibility of achieving specific antitumor effects induced by fused apoptosis-enhancing proteins.
引用
收藏
页码:205 / 213
页数:9
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