OK-432联合IL-2对C_(57)BL/6小鼠Lew is肺癌的抑制作用及p21的表达

Effect of OK-432 Combination with IL-2 on Inhibiting Lew is Lung Cancer Growth and Expression of P_(21) in C_(57)BL/6 mice

目的 研究 OK- 432与 IL - 2抑制近交系小鼠 C5 7BL / 6 L ewis肺癌 (L L C)的生长及 p2 1的表达。 方法 以 C5 7BL / 6荷瘤 L L C小鼠为模型 ,观察 OK- 432联合 IL - 2对肿瘤发生、生长、转移的影响 ,体内对肿瘤细胞的作用及用抗鼠 p2 1单克隆抗体进行 SABC免疫组化技术半定量测定 p2 1在 L ewis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 5 ) ,肺转移灶数目明显减少。电镜下显示肿瘤灶中出现许多凋亡细胞 ,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。 p2 1在联合用药组表达明显减少。 结论 OK- 432与 IL - 2有明显的协同抗肿瘤活性 ,其杀瘤过程主要为对瘤细胞的直接或间接攻击 ,部位原因可能阻抑 ras癌基因的激活 ,诱导瘤细胞凋亡 ;提示 OK- 432联合 IL -

Objective To study the eftect of OK-432 and IL-2 on inhibiting Lewis lung cancer(LLC) growth and p21 expression in inbred CBL/6mice. Methods As C 57 BL/6 mice bearing LLC model, to observed OK-432 combination IL-2 effect on the tumor occurrence, growth, metastasis, tumor cell changes in vivo, and used the monoclonal antibody to p21 and SABC immunohistochemical method, the expression of p21 in primary tumor tissues was semiquantitatively determined. Result Combination administration group significantly enhaneed inhibition effect on tumor volume and weight versus control(P<0 01), increased inhibition rate (P<0 05), and distinctly reduced the number of pulmonary metastasis focus. Under electron microscope, a lot of apoptosis cell emerged in the tumor focus, tumor cell emerged karyopyknosis, new-moonth shaped or circular, nucleus membrane was clear, endoplasmic reticulum was dilation, and mitochondrion was swelling. The expression of p21 significantly decreased in combination group verus control group. Conclusion OK-432 and IL-2 had distinctly synergetic anti-tumor effect, the process of their killing tumor might mainly attack the tumor cell directly or indirectly, partly due to inhibit ras ongene activation, and induced tumor cell apoptosis. the results showed that OK-432 combination IL-2 might be an effcient biotherapy means to cancer patients clinically.