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

基因芯片检测结果显示，与敏感细胞相比，耐药细胞中AKR 1C家族表达均上调。我们用AKR 1C siRNA或特异性AKR 1C抑制剂甲芬那酸处理化疗耐药细胞。在体内，甲芬那酸和CDDP/5-FU联合治疗的抗肿瘤生长作用大于单独的甲芬那酸或单独的CDDP/5-FU。结论：顺铂、5-FU联合甲芬那酸治疗耐药口腔鳞癌是一种有效的治疗方案。对顺铂/5-氟尿嘧啶与甲芬那酸联合治疗的体内、外毒性进行了评价，以确定其临床应用的安全性。

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.