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

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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.