Development of cancer treatment by molecular targeted anti-cancer hybrid peptide against refractory cancers which are resistant to cancer chemotherapy

通过分子靶向抗癌杂合肽开发针对对癌症化疗耐药的难治性癌症的癌症治疗

• 批准号: 23680089
• 负责人: KAWAKAMI Koji
• 金额: $ 17.56万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (A)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23680089/
• 关键词: 分子標的治療; ペプチド創薬; ハイブリッドペプチド; 難治性癌; 治療抵抗性

We focused on the targeting to transferrin receptor, IL4 receptor alpha, Neuropilin-1, and Her2 which over-express on the refractory cancer cells including pancreatic cancer and glioblastoma, and designed hybrid peptide in which targeting peptides to these receptors were conjugated with lytic type peptide that disintegrates selectively cancer cell membrane. It was found that designed hybrid peptides had effective cytotoxic and anti-tumor activities toward cancer cells over-expressing these receptors including resistant cell lines to trastuzumab and lapatinib both in vitro and in vivo. Thus, it is suggested that hybrid peptide designed in this study may provide a potent therapeutic option for patients with refractory cancer in the future.

我们专注于靶向转铁蛋白受体、IL 4受体α、神经纤毛蛋白-1和Her 2，这些受体在包括胰腺癌和胶质母细胞瘤在内的难治性癌细胞上过表达，并设计了杂合肽，其中靶向这些受体的肽与选择性分解癌细胞膜的裂解型肽缀合。发现设计的杂合肽在体外和体内对过表达这些受体的癌细胞（包括对曲妥珠单抗和拉帕替尼具有抗性的细胞系）具有有效的细胞毒性和抗肿瘤活性。因此，本研究中设计的杂合肽可能为未来难治性癌症患者提供有效的治疗选择。

项目成果

抗癌ペプチドLyticの細胞における作用機序に関する研究

抗癌肽Lytic在细胞内的作用机制研究

• 发表时间: 2012
• 作者: 大原弘路;河野雅之;川上浩司
• 通讯作者: 川上浩司

Molecular mechanism of cytotoxicity induced by Hsp90-targeted Antp-TPR hybrid peptide in glioblastoma cells.

胶质母细胞瘤细胞中HSP90靶向的ANTP-TPR杂交肽诱导的细胞毒性的分子机制。

• DOI: 10.1186/1476-4598-11-59
• 发表时间: 2012-08-22
• 期刊: Molecular cancer
• 影响因子: 37.3
• 作者: Horibe T;Torisawa A;Kohno M;Kawakami K
• 通讯作者: Kawakami K

Entry of a cationic lytic-type peptide into the cytosol via endocytosis-dependent and–independent pathways in human glioma U251 cells

人神经胶质瘤 U251 细胞中阳离子裂解型肽通过内吞作用依赖性和独立途径进入细胞质

• DOI: 10.1016/j.peptides.2013.09.015
• 发表时间: 2013
• 期刊: Peptides
• 影响因子: 3
• 作者: Ohara;K.;Kohno;M.;Hamada;T.;and Kawakami;K
• 通讯作者: K

Functional analysis of cytotoxic activity to glioblastoma cells by Antp-TPR hybrid peptide targeting Hsp90

靶向 Hsp90 的 Antp-TPR 杂合肽对胶质母细胞瘤细胞的细胞毒活性的功能分析

• 发表时间: 2013
• 作者: Horibe;T. and Kawakami;K
• 通讯作者: K

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