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Molecular Therapy Targeting PTEN-Akt Signaling Pathway in Prostate Cancer.

前列腺癌中针对 PTEN-Akt 信号通路的分子治疗。

基本信息

批准号：
17591697
负责人：
TANAKA Motoyoshi
金额：
$ 2.3万
依托单位：
Kinki University (2006)Nara Medical University (2005)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

1. Exploration of molecular markers for prostate cancer : To evaluate the new molecular marker of prostate cancer, we examined the expression of PTEN, phospho-Akt, Bcl-2, and VEGF as down stream of Akt-PTEN signaling pathway in prostate cancer specimens from the operation by immunohistochemistry. These molecules expression status revealed as a possible prognostic or response marker of chemotherapy, radiotherapy, or hormone therapy.2. Sleeping beauty transposon plasmid vector as drug design : Sleeping beauty (SB) transposon is a system to integrate the gene into choromosome. We designed a cationized hydrogelatin conjugated with SB aiming for slow releasing compound, which can last long term gene expression in vivo, and observed successful gene transduction of SB vector system in mouse system.3. Molecular therapy with transporter protein or peptide : We developed a transporter system of antibody and functional peptide in treating prostate cancer. P16 and p14 functional peptides were shown to inhibit tumor cell growth of prostate cancer cells in vitro. Antibody of p-Akt as protein was also shown to work in vitro for the treatment of prostate cancer cells.4. In vivo experiment : Subcutaneous tumor model in nude mice were examined if we can treat with conjugation of cationized gelatin and SB or peptide. P16 and p14 functional peptide treatment showed a significant tumor growth inhibition in nude mice and sensitized radiotherapy combination. Now we are repeating these animal experiment.

1.前列腺癌分子标志物的探索：为了评估前列腺癌的新分子标志物，我们通过免疫组织化学方法检测了来自手术的前列腺癌标本中PTEN、磷酸化Akt、Bcl-2和作为Akt-PTEN信号通路下游的VEGF的表达。这些分子的表达状态可能作为化疗、放疗或激素治疗的预后或反应指标.作为药物设计的睡美人转座子质粒载体：睡美人转座子是将基因整合到染色体中的系统。设计了一种能在体内持续表达的SB缓释复合物，并在小鼠体内成功地观察到SB载体系统的基因转导.转运蛋白或转运肽的分子治疗：我们开发了一种抗体和功能肽的转运系统，用于治疗前列腺癌。P16和P14功能肽在体外显示出抑制前列腺癌细胞的肿瘤细胞生长。p-Akt抗体作为蛋白质在体外也显示出对前列腺癌细胞的治疗作用.体内实验：采用裸鼠皮下移植瘤模型，观察阳离子明胶与SB或肽的偶联物对肿瘤的治疗效果。P16和p14功能肽治疗在裸鼠和致敏放疗联合中显示出显著的肿瘤生长抑制作用。现在我们重复这些动物实验。