Study on differentiation therapy of prostatic cancer

前列腺癌的分化治疗研究

• 批准号: 09671606
• 负责人: MIZUTANI Takashi
• 金额: $ 1.86万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671606/
• 关键词: prostatic cancer; differentiation therapy; LNCaP; papaverine; cyclic AMP; 分化誘導療法; プロスタグランジンE_2; 神経内分泌細胞

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.

用磷酸二酯酶抑制剂罂粟碱、3-异丁基-1-甲基黄嘌呤（IBMX）或茶碱中的一种处理三种人前列腺癌细胞系PC-3、DU 145和LNCaP 6天。在所检测的3种药物中，罂粟碱（10 μ g/L D1-5 μ g/L D1 M）是LNCaP细胞中形态变化和细胞内环AMP水平升高的最有效诱导剂。LNCaP细胞看起来像神经内分泌细胞，其特征在于罂粟碱处理后的小细胞体和长突起。流式细胞仪细胞周期分析显示罂粟碱处理的LNCaP细胞被阻滞在G 0/G1期。蛋白质印迹分析显示LNCaP细胞强烈表达神经元标记物AchE。罂粟碱在mRNA和蛋白水平上显著抑制LNCaP细胞中PSA的分泌和表达。此外，通过细胞计数和Matrigel侵袭室测定法测量的LNCaP细胞的增殖和侵袭潜力被罂粟碱显著抑制。结果表明，罂粟碱诱导LNCaP细胞的终末分化，这与细胞内环AMP介导的途径相关。总之，这些研究结果表明，诱导细胞分化的药物，包括罂粟碱，可能是有用的治疗晚期前列腺癌患者。

项目成果

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)

Matsushima H、Kitamura T、Goto T、Hosaka Y、Homma H 和 Kawabe K.：“bcl-2 和 p53 免疫染色的联合分析预测前列腺癌的预后较差。”J Urol。

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)

Goto T、Tanaka Y、Matsushima H、Homma Y、Hosaka Y 和 Kawabe K.：“Rerum Eiken 前列腺特异性抗原水平在预测前列腺癌前列腺切除术后复发中的意义。”Hinyokigeka。

Hisashi Matsushima: "Immunohistochemical study of p21^<WAFI> and p53 proteins in prortatic cancer and their prognostic significance" Human PATHOLOGY. 29・8. 778-783 (1998)

Hisashi Matsushima：“前列腺癌中 p21^<WAFI> 和 p53 蛋白的免疫组织化学研究及其预后意义”人类病理学 29・8 (1998)。

Hisashi Matsushima: "Correlation between proliteration,apoptosis,and angiogenesis in prostate corcinoma and their rel*tion to androgen ablation"Cancer. 85. 1822-1827 (1999)

Hisashi Matsushima：“前列腺癌增殖、凋亡和血管生成之间的相关性及其与雄激素消融的关系”癌症。

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)

Toshitaka Goto：“罂粟碱对人前列腺癌 LNC*P 细胞形态分化、增殖和侵袭潜力的影响”国际泌尿学杂志。