p53 protein transduction therapy: Successful targeting and inhibition of the growth of the bladder cancer cells
p53 protein transduction therapy: Successful targeting and inhibition of the growth of the bladder cancer cells
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DOI：
10.1016/j.eururo.2005.08.019
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发表时间：
2006-01-01
期刊：
影响因子：
23.4
通讯作者：
Matsui, H
中科院分区：
文献类型：
--
作者：
Inoue, M;Tomizawa, K;Matsui, H
前言：病毒介导的膀胱癌基因治疗存在基因传递效率和安全性等问题。我们已经报道了多聚精氨酸肽(11R)具有增加细胞内蛋白质转导的能力。在这里，我们展示了使用11R进行P53蛋白转导。材料和方法：将11R-P53融合蛋白(11R-P53)导入膀胱癌细胞株J82和T24中，观察其抗肿瘤作用。用4-[3-(4-碘苯基)2-(4-nitrophenyl)-2H-5-tetrazolio]-1，3-benzene二磺酸盐(WST)法检测细胞存活率。为探讨11R-P53对抗癌药物依赖性膀胱癌细胞凋亡的影响，将11R-P53与顺铂(CDDP)共同作用于膀胱癌细胞株。Hoechst染色鉴定凋亡细胞。为了探讨11R介导的蛋白转导在膀胱肿瘤中的作用，将J82细胞移植到SCID小鼠体内，并将11R-GFP经尿路导入膀胱内。结果：11R-P53对J82和T24细胞的生长均有抑制作用，且呈剂量依赖性。11R-P53的转导增强了CDDP依赖的细胞凋亡诱导。结论：P53蛋白转导治疗膀胱癌可能是一种很有前途的治疗方法。(C)2005 Elsevier B.V.保留所有权利。
Introduction: Virus-mediated gene therapy for bladder cancer has some problems, such as efficiency of gene delivery and safety issues. We have reported that poly-arginine peptide (11R) has the ability to increase protein transduction in cells. Here, we show that p53 protein transduction using 11R. is useful for targeting to bladder tumors and suppressing the growth of bladder cancer cells.Materials and methods: An 11R-fused p53 protein (11R-p53) was transduced in bladder cancer cell lines (J82 and T24) to evaluate the anti-tumor effect. Cell viability was assessed by performing the 4- [3-(4-iodophenyl) 2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST) assay. To investigate whether 11R-p53 enhanced the effect on anti-cancer drug-dependent apoptosis of bladder cancer cells, the cell lines were cotreated with 11R-p53 and cis-diaminedichloroplatinum (CDDP). Apoptotic cells were identified using Hoechst staining. To investigate the efficiency of protein transduction mediated by 11R in bladder tumors in vivo, SCID mice were transplanted with J82 cells in the bladder and 11R-GFP was transurethrally transduced into the bladder. The transduction of 11R-GFP in the tumor was examined by confocal microscopy.Results: 11R-p53 inhibited the growth of both J82 and T24 cells in a dose-dependent manner. The transduction of 11R-p53 enhanced CDDP-dependent induction of apoptosis. Transurethral application of 11R-GFP resulted in transduction of GFP in bladder tumors but not in the normal bladder epithelium or subepithelial tissues.Conclusion: The present results suggest that p53 protein transduction therapy may be a promising method for the treatment of bladder cancer. (c) 2005 Elsevier B.V. All rights reserved.