PI3-K抑制剂LY294002增强丝裂霉素C对大鼠原位膀胱癌抑制作用的研究

In vivo bladder cancer growth inhibition by a phosphatidylinositol 3-kinase inhibitor(LY294002)

目的研究PI3-K抑制剂LY294002在大鼠体内应用时对膀胱灌注化疗药物丝裂霉素C(mitomycin C,MMC)的协同抑癌作用以及毒副作用。方法对荷原位膀胱癌的大鼠进行膀胱内灌注生理盐水、MMC、LY294002,记录大鼠体重变化、CT动态观察膀胱肿瘤变化、处死后直接测量膀胱肿瘤大小及观察灌注治疗完成后的存活率。结果 MMC联合LY294002灌注治疗4周后,荷膀胱癌大鼠平均体重明显高于单独MMC治疗组,CT扫描显示MMC联合LY294002灌注治疗对膀胱肿瘤的抑制作用强于单独MMC灌注。MMC联合LY294002灌注治疗4周后,大鼠膀胱内肿瘤直径小于单独MMC灌注组。灌注治疗4周后,各组大鼠存活率差异无统计学意义。LY294002灌注治疗会导致大鼠一过性的体重下降,无其他严重不良反应发生。结论 LY294002能增强MMC对大鼠膀胱癌的抑制作用,LY294002在大鼠体内应用时无严重不良反应发生。

Objective To study the antitumor effect of intravesically instillation of MMC plus LY294002 in vivo.Methods The rats with orthotopic bladder cancer were administrated intravesically with normal sodium,MMC or MMC plus LY294002 within consecutive 4 weeks.The weights of rats were continuously recorded.The bladder tumors of rats were evaluated by CT scanning before and after intravesical administration.The sizes of the bladder tumors were measured after the administrations were completed.Results After administration intravecical with normal sodium,MMC or MMC plus LY294002,the weights of rats in MMC plus LY294002 group were higher than the weights of rats in MMC only group,and the tumor sizes of rats in MMC plus LY294002 group were less than the sizes of rats in MMC only group.CT outcomes showed that regression of tumor in MMC plus LY294002 group were better than MMC only group.Conclusions LY294002 enhanced the antitumor effect of MMC and has not serious side effect in vivo.