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

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。

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.