【摘要】 目的:探讨OK-432增强CPT-11抗肿瘤活性的机制。方法:将荷B16黑色素瘤的C57BL/6小鼠随机分为对照组、CPT-11治疗组、联合治疗组,于接种后第3天腹腔分别注射生理盐水、CPT-11、CPT-11加OK-432。观察肿瘤生长体积;测定各组脾细胞分泌的IL-2、IL-4、IL-6、IL-10、IL-12、IFN-γ,并在体外观察了SN-38对OK-432刺激这些细胞因子分泌的影响。结果:OK-432显著增强CPT-11对B16黑色素瘤生长的抑制(P<0.05);CPT-11在体内显著抑制小鼠脾细胞IL-12和IFN-γ的分泌,与OK-432联合使用显著增加小鼠脾细胞IL-2、IL-6、IL-12和IFN-γ的分泌(P<0.05);在体外SN-38对OK-432刺激的IL-6、IL-12分泌无显著影响(P>0.05)。结论:OK-432在体内可通过刺激IL-12和Th1细胞因子的分泌,增强CPT-11的抗肿瘤活性。更多还原

【Abstract】 Objective:To assess the potential mechanisms of the antitumor activities of Irinotecan(CPT-11)enhanced by the streptococcal preparation OK-432.Methods:C57BL/6mice were transplated subcutaneously with5×10 5 B16melanoma cells and randomized into3groups.Three days after the inoculation,the mice were respectively treated with saline(control),CPT-11and CPT-11plus OK-432intraperitoneally3days per week for3weeks.The tumor growth size of mouse was measured biweekly and the effects on IL-2,IL-4,IL-6,IL-10,IL-12and IFN-γproduction of mouse splenocyte was investigated.Furthermore,the effect of SN-38(the active metabolite of CPT-11)on the cytokines production of mouse splenocyte when stimulat-ed with OK-432was also investigated in vitro.Results:OK-432significantly enhanced the in-hibiting effect of CPT-11on B16melanoma growth(P<0.05).CPT-11administration principally inhibited IL-12and IFN-γproduction of mouse splenocyte,while combined with OK-432admin-istration significantly increased the production of IL-2,IL-6,IL-12and IFN-γ(P<0.05).When stimulated with OK-432in vitro,the production of IL-2,IL-6,IL-12and IFN-γof splenocyte derived from combined treatment group increased remarkedly as compared with CPT-11treatment group(P<0.05).In vitro SN-38showed a dose-dependent inhibition on IFN-γand IL-10pro-duction of mouse splenocyte induced by OK-432,but little influence on the production of IL-12 and IL-6.Conclusion:OK-432could stimulate IL-12and Th1cytokines production and effec-tively enhance the antitumor activity of CPT-11.更多还原