New strategy of intravesical in stillation using anti-cancer peptide for bladder tumor

抗癌肽膀胱灌注治疗膀胱肿瘤新策略

• 批准号: 21592031
• 负责人: SHIMAZUI Toru
• 金额: $ 2.91万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592031/
• 关键词: 腫瘍学; 膀胱癌; ペプチド導入; p16; トランスポーターペプチド; マウス; BBN発癌

P16, which is a key molecule of bladder tumor (BT) development, inhibits the tumor growth through maintaining the retinoblastoma protein (Rb) in its hypophosphorylated state. In clinical samples, it is reported that abnormal p16 was observed in approximately 70% of human BT. In this study, we investigated whether or not new peptide transporter system using Wr-T with minimum inhibitory sequence peptide of p16 (p16-MIS) could inhibit growth of BT. In vitro, peptide transfer with p16-MIS successfully inhibit the human and mouse bladder tumor cell line with absent p16 and phosphorylated Rb. In the in vivo study, both local and systemic administration of p16-MIS using Wr-T system inhibited the growth of subcutaneous BT graft in mice. In histological examination, p16-MIS transfer decreased the Rb phosphorylation and induced the apoptosis. Although animal model for intravesical transplantation of BT should be established, peptide transporter with p16-MIS and Wr-T might become a possible new treatment strategy by intravesical instillation.

P16是膀胱肿瘤（BT）发生发展的关键分子，通过维持视网膜母细胞瘤蛋白（Rb）的低磷酸化状态来抑制肿瘤生长。在临床样本中，据报道，在约70%的人BT中观察到异常p16。在本研究中，我们研究了新的肽转运蛋白系统是否使用p16的最小抑制序列肽（p16-MIS）的BMP-T可以抑制BT的生长。在体外，肽转移与p16-MIS成功地抑制人和小鼠膀胱肿瘤细胞系与缺乏p16和磷酸化Rb。在体内研究中，局部和全身施用p16-MIS使用BTA-T系统抑制小鼠皮下BT移植物的生长。在组织学检查中，p16-MIS转染降低Rb磷酸化并诱导凋亡。虽然BT膀胱内移植的动物模型尚待建立，但p16-MIS和p16-T联合肽转运蛋白膀胱内灌注可能成为一种新的治疗策略。

项目成果

Supression of AhR signaling pathway is associated with the down-regulation of UDP-glucuronosyltransferases during BBN-induced urinary bladder carcinogenesis in mice.

在 BBN 诱导的小鼠膀胱癌发生过程中，AhR 信号通路的抑制与 UDP-葡萄糖醛酸基转移酶的下调相关。

• 发表时间: 2009
• 期刊: J Biochem 147
• 作者: Iida K;Shimazui T;et al.
• 通讯作者: et al.

機能性ペプチド導入による腎細胞癌に対する新しい分子標的治療

引入功能肽治疗肾细胞癌的新分子靶向治疗

• 发表时间: 2010
• 作者: 全並賢二;島居徹;他
• 通讯作者: 他

Low expression of microphthalmia-associated transcription factor, a potential molecular target for interferon-alpha susceptibility, is associated with metastasis in renal cell carcinoma.

小眼相关转录因子的低表达是干扰素-α敏感性的潜在分子靶标，与肾细胞癌的转移相关。

• 发表时间: 2009
• 期刊: Cancer Sci. 100
• 作者: Shimazui T;Kojima T;Uchida;et al.
• 通讯作者: et al.

A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system

使用新型转运系统的 p16 功能肽治疗肾细胞癌的新分子靶向治疗方法

• 发表时间: 2011
• 期刊: Oncol Rep.
• 作者: Zennami K;Yoshikawa K;Kondo E,;De Velasco MA;Tanaka M;Uemura H;et al.
• 通讯作者: et al.

Systemic transduction of p16INK4A anti-tumor peptide inhibits growth of MBT-2 bladder tumor cell linegraft in mice

p16INK4A 抗肿瘤肽的全身转导抑制小鼠 MBT-2 膀胱肿瘤细胞系移植物的生长

• 发表时间: 2011
• 作者: Shimazui T;et al
• 通讯作者: et al