Development of enhancement chemotherapy by overcoming an anti-cancer resistant mechanism of AKR1C family

克服AKR1C家族抗癌机制开发强化化疗

• 批准号: 23659936
• 负责人: SHIIBA Masashi
• 金额: $ 2.25万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659936/
• 关键词: アルドースケトース還元酵素; 口腔癌; マイクロアレイ解析; 抗癌剤多剤耐性遺伝子; アルドケトース還元酵素(AKR); 抗癌剤耐性; メフェナム酸; アルドース‐ケトース還元酵素（AKR）

Using microarray analysis, AKR1C family were up-regulated in all CDDP-resistant cell lines compared with CDDP-sensitive cell lines. We treated the chemoresistant cells with AKR1C siRNA or specific AKR1C inhibitor, mefenamic acid. In vivo, the antitumor growth effect of the combination therapy of mefenamic acid and CDDP/5-FU was greater than that with either mefenamic acid alone or CDDP/5-FU alone. In conclusion, combination CDDP and5-FU chemotherapy with mefenamic acid might be a great therapeutic system for chemoresistant OSCC. Toxicity of combination therapy of CDDP/5-FU and mefenamic acid was evaluated in vitro and in vivo, resulting in the recognition of the safety for the clinical application.

通过芯片分析，与cddp敏感细胞系相比，AKR1C家族在所有cddp耐药细胞系中均上调。我们用AKR1C siRNA或特异性AKR1C抑制剂甲氧胺酸处理化疗耐药细胞。在体内，甲氧胺酸与CDDP/5-FU联合治疗的抗肿瘤生长效果大于单用甲氧胺酸或单用CDDP/5-FU。综上所述，CDDP联合5- fu联合甲氧胺酸可能是化疗耐药OSCC的一个很好的治疗方案。体外和体内评价了CDDP/5-FU与甲氧胺酸联合治疗的毒性，对临床应用的安全性进行了肯定。