OK-432联合IL-2对Lewis肺癌及c-fos蛋白表达的抑制作用

The Inhibitory Effect of OK-432 and IL-2 on Lewis Lung Cancer Growth and c-fos Expression

目的 研究OK 4 32与IL 2抑制近交系小鼠C57BL/6Lewis肺癌 (LLC)的生长及c fos蛋白的表达。方法 以C57BL/6荷瘤LLC小鼠为模型 ,观察OK 4 32联合IL 2对肿瘤发生、生长转移的影响 ,及用抗鼠c fos单克隆抗体进行SABC免疫组化技术半定量测定c fos在Lewis肺癌原发灶中的表达。结果 二者联用对肿瘤体积和重量的抑制作用明显增强 (P <0 0 1) ,增强抑瘤率 (P <0 0 1) ,肺转移灶数目明显减少。光镜下显示肿瘤灶中出现许多凋亡细胞 ;肿瘤组织电镜观察 ,瘤细胞核染色质浓集成块 ,在核膜内呈新月形或环形排列 ,核膜清楚 ,瘤细胞内质网扩张 ,线粒体肿胀。c fos在联合用药组与对照组比较明显减少 (P <0 0 1)。结论 OK 4 32与IL 2有明显的协同抗肿瘤活性 ,部分原因可能阻抑c fos基因的表达 ;提示OK 4 32联合IL 2可望为临床治疗癌症患者提供一种有效的生物治疗方法。

Objective To study the inhibitory effect of OK-432 and IL-2 on the growth of Lewis lung cancer (LLC) bearing C 57 BL/6 mice and c-fos protein expression.Methods As C 57 BL/6 mice bearing LLC model,we observed the effect of OK-432 in combination with IL-2 on the tumor occurrence,growth,metastasis,and the expression of c-fos by using the semiquantitative SABC immunohistochemical method.Results Combination group significantly enhanced inhibitory effect on tumor volume and weight versus control( P <0.01),increased inhibitory rate( P <0.01),and distinctly reduced the number of pulmonary metastasis loci.A lot of apoptosis cells emerged in the tumor loci under light microscope,under electron microscope,tumor cells emerged karyopyknosis,new-moonth shaped or circular,nucleus membrane was clear,endoplasmic reticulum was dilation,and mitochondrion was swelling.The expression of c-fos significantly decreased in combination group verus control group ( P <0.01).Conclusion OK-432 and IL-2 had significantly synergetic anti-tumor effect,partly because of inhibiting c-fos gene expression.The results showed that OK-432 in combination with IL-2 might be an efficient biotherapy means for treatment of cancer patients.