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1998 Fiscal Year Final Research Report Summary

Study on differentiation therapy of prostatic cancer

Research Project

Project/Area Number 09671606
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionThe University of Tokyo

Principal Investigator

MIZUTANI Takashi  The University of Tokyo Hospital Intemal Medicine Assistant Professor, 医学部・附属病院, 助手 (50199999)

Co-Investigator(Kenkyū-buntansha) HOSAKA Yoshio  The University of Tokyo Hospital Intemal Medicine Associate Professor, 医学部・附属病院(分), 助教授 (70133080)
KITAMURA Tataishi  The University of Tokyo Hospital Intemal Medicine Professor, 医学部・附属病院, 教授 (70010551)
Project Period (FY) 1997 – 1998
Keywordsprostatic cancer / differentiation therapy / LNCaP / papaverine / cyclic AMP
Research Abstract

Three human prostate cancer cell lines PC-3, DU145 and LNCaP were treated with one of the phosphodiesterase inhibitors papaverine, 3-isobutyl-1-methylxanthine (IBMX) or theophylline for 6 days. Of the 3 agents examined papaverine (10ィイD1-5ィエD1 M) is the most effective inducer of morphologic change and raised intracellular cyclic AMP levels in LNCaP cells as well. LNCaP cells appears like neuroendocrine cells, characterized by small cell bodies and long processes after papaverine treatment. Flow cytometric cell cycle analysis showed that LNCaP cells treated with papaverine were arrested in G0/G1. LNCaP cells showed intense expression of neuronal marker AchE by western blot analysis. Papaverine significantly inhibits PSA secretion and expression both at the mRNA and protein levels in LNCaP cells. Additionally, proliferation and invasive potential of LNCaP cells measured by cell counting and the MatrigelィイD1TMィエD1 invasion chamber assay were significantly inhibited by papaverine. The results suggest that papaverine induces terminal differentiation in LNCaP cells, which is correlated with an intracellular cyclic AMP-mediated pathway. In conclusion, these findings suggest that agents which induce cellular differentiation, including papaverine, may be useful in treating patients with advanced prostate cancer.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Hisashi Matsushima: "Combined analysis with Bcl-2 and p53 immunostaining predicts poorer prognosis in prostatic carcinoma"The Journal of Urology. 158. 2278-2283 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hisashi Matsushima: "Immunohistochemical study of p21WAP1 and p53 proteins in prostatic cancer and their prognostic significance"Human PATHOLOGY. 29. 778-783 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 後藤智隆: "前立腺全摘術後の血清Eiken PSA値と前立腺癌の再発に関する検討"泌尿器外科. 11. 1415-1419 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hisashi Matsushima: "Correlation between proliteration,apoptosis,and angiogenesis in prostate corcinoma and their rel*tion to androgen ablation"Cancer. 85. 1822-1827 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toshitaka Goto: "The affect of popaverine on morphologic differentiation,proliteration,and invasive potential of human prostatic cancer LNC*P cells"International Journal of Urology. 6. 314-319 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsushima H, Kitamura T, Goto T, Hosaka Y, Homma H and Kawabe K.: "Combined analysis with bcl-2 and p53 immunostaining predicts poorer prognosis in prostatic carcinoma."J Urol. 158. 2278-2283 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsushima H, Sasaki T, Goto T, Hosaka Y, Homma H, Kitamura T, Kawabe K, Sakamoto A, Muramami T and Machinami R.: "Immunohistochemical study of p21ィイD1WAF1ィエD1 and p53 proteins in prostatic cancer and their prognostic significance."Hum Pathol. 29. 778-783 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Goto T, Tanaka Y, Matsushima H, Homma Y, Hosaka Y and Kawabe K.: "The significance of rerum Eiken prostate specific antigen level in prediction of post prostatectomy recurrence of prostate cancer."Hinyokigeka. 11. 1415-1419 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsushima H, Goto T, Hosaka Y, Kitamura T and Kawave K.: "Correlation between proliferation, apoptosis, and angiogenesis in prostate carcinoma and their relation to androgen ablation."Cancer. 85. 1822-1827 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Goto T, Matsushima H, Kasuya Y, Hosaka Y, Kitamura T, Kawabe K, Hida A, Ohta Y, Simizu T and Takeda K.: "The effect of papaverine on morphologic dirrerentiation, proliferation and invasive potential of human prostatic cancer LNCaP cells."Int J Urol. 6. 314-319 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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