环磷酰胺衍生物SLXM-2对小鼠脑瘤B_(22)的抗肿瘤作用及机制

Antitumor effect and mechanism of the cyclophosphamide derivative SLXM-2 on B_(22) brain tumor in mice

目的:研究环磷酰胺衍生物SLXM-2对小鼠脑瘤B22的抗肿瘤作用及对小鼠免疫系统的影响,并探讨其抑瘤作用的分子机制。方法:采用小鼠脑瘤B22移植性肿瘤模型评价SLXM-2的抑瘤作用,测定免疫器官的脏器指数和白细胞数量;通过Western Blot检测SLXM-2对细胞周期相关蛋白表达的影响。结果:20,40 mg.kg-1 SLXM-2对小鼠脑瘤B22的抑瘤率分别为11.5%和53.9%;与阴性对照组相比,SLXM-2对小鼠免疫器官的脏器指数及白细胞数量无明显影响,可上调p53,p21,CDK7,Wee1,p-Cdc2(Tyr15),p-Cdc2(Thr 161)和CyclinB1等蛋白表达,下调CyclinE的表达,Cdc2,CDK2和Cdc25C表达水平变化不明显。结论:SLXM-2对小鼠脑瘤B22的生长有一定抑制作用,对小鼠免疫器官指数和白细胞数量没有影响;SLXM-2的抗肿瘤机制与调节p53,p21,Wee1,p-Cdc2(Tyr15)和CyclinE等蛋白表达有关。

Objective： To investigate the antitumor effect of SLXM-2, a derivative of cyclophosphamide, on B22 brain tumor in mice, its immune toxicity, and the possible anticaneer mechanism. Methods： A mouse mod- el of B2z brain tumor was used to evaluate anticancer effect of SLXM-2. Immune organs indices were calculated and the number of white blood cells （WBC） was detected. The expression of cell cycle-related proteins was detected by Western blot. Results ： After treatment with 20 and 40 mg·kg-1 SLXM-2, the inhibition rate of tumor growth were 11.5% and 53.9%. Compared with negative control, the immune organ indices and the number of WBC of SLXM- 2 group had no significant difference. The expressions of p53, p21, CDK7, Weel, p-Cde2 （Tyrl5） , p-Cde2 （Thr 161 ） and CyelinB1 were up-regulated; those of Cdc2, CDK2 and Cde25C had no significant difference; the expression of CyelinE was down-regulated. Conclusion ： SLXM-2 inhibits the growth of B22 brain tumor in mice and has no influence on immune organ indices and the amount of WBC. The antieaneer mechanism of SLXM-2 is related to the changes in p53, p21, Weel, p-Cde2 （Tyrl5） and CyelinE expression.