Cen-Penetrating D-IsomerPeptidesofp53C-Terminus: Long-term Inhibitory Effect on the Growth of Bladder Cancer
| Project/Area Number |
20591856
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Okayama University |
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Principal Investigator |
WATANABE Toyohiko Okayama University, 岡山大学病院, 講師 (30432644)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIAZAWA Kazuhito 熊本大学, 大学院・生命科学研究部, 教授 (40274287)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 細胞 / 組織 / 細胞・組織 |
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| Research Abstract |
OBJECTIVES To investigate whether a single application of the membrane-permeable D-isomer of the p53 C-terminus connected with a retro-inverso version of the NH2-terminal 20-amino acid peptide of the influenza virus hemagglutinin-2 protein (riHA2) inhibited the growth of bladder cancer cells. The transduction of p53 using poly-arginine is useful for targeting and suppressing the growth of bladder cancer cells. However, the protein's intracellular half-life is short, and repeated application is necessary to achieve an anti-tumor effect.
METHODS The p53 carboxyl-terminal peptides covalently coupled with cell-penetrating peptides were synthesized with D- or L-amino acids. Moreover, the peptides were connected with riHA2 by a disulfide bridge. Human bladder cancer cell lines were incubated with each peptide and cell viability was assessed with the WST assay. Apoptotic cells were confirmed by Hoechst and active capase-3 staining. The p53 peptides were injected into severe combined immunodeficiency disease mice transplanted with J82 cells to investigate their anti-tumor effect on bladder tumors. A survival curve was plotted using the Kaplan?Meier method.
RESULTS A single application of cell-penetrating D-isomer peptides of the p53 C-terminus connected with riHA2 (d11R-p53C=-riHA2 and dFHV-p53C=-riHA2) inhibited the growth and induced the apoptosis of bladder cancer cells. The tumor-bearing mice treated only with vehicle had a mean survival time of 12 days, whereas treatment with d11R-p53C=-riHA2 resulted in a long-term survival rate of 50%.
CONCLUSIONS Peptide transduction therapy using the D-isomer p53 C-terminal peptide with riHA2 may be an innovative method for the treatment of bladder cancer.
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Report
(4 results)
Research Products
(11 results)
