奥沙利铂结合CIK细胞对人胃癌裸鼠腹膜移植模型体内抗肿瘤作用的实验研究

Anti-tumor effects of L-OHP and CIK cells on transplantable peritoneal metastasis of human gastric cancer in nude mice

目的比较单独应用奥沙利铂(L-OHP)、细胞因子诱导的杀伤(CIK细胞)和L-OHP联合CIK细胞对人胃癌裸鼠腹膜移植瘤生长的抑制作用,为临床上联合应用L-OHP和CIK细胞治疗胃癌提供实验依据。方法通过提取健康供血者的PBMC,分别加入γ-IFN、IL-2、抗-CD3单克隆抗体和IL-1培养CIK细胞;用药效学体内实验法和病理形态学方法分别观察正常对照组、生理盐水对照组、不同剂量的L-OHP组、不同剂量的CIK细胞组和L-OHP+CIK组对人胃癌裸鼠腹膜移植模型的体内抗肿瘤作用。结果与NS对照组相比,L-OHP组(1.125、2.25mg/kg)、CIK细胞组[(1～2)×108mL-1]组人胃癌裸鼠腹膜移植模型治疗后生存期均明显延长,腹围明显减小(P<0.01);L-OHP+CIK组人胃癌裸鼠腹膜移植模型治疗后生存期进一步明显延长,腹围明显减小(P<0.01),与正常对照组相比,上述指标无明显差异(P>0.01)。病理形态学结果显示,L-OHP组、CIK细胞组及L-OHP+CIK组癌细胞坏死、凋亡改变逐渐加重。结论L-OHP联合CIK细胞对人胃癌裸鼠腹膜移植瘤生长的抑制作用大于单独应用L-OHP或CIK细胞。

Objective To investigate anti-tumor effect of L-OHP and C1K cells on transplantable peritoneal metastasis of human gastric cancer in nude mice. Methods CIK cells were obtained by incubation of peripheral blood mononuclear cells （PBMCs） from healthy donors with cytokinesin vitro. With comparison of NS, the anti-tumor effects of L-OHP, CJK cells, and L-OHP ＋ CIK cells on transplantable peritoneal metastasis of human gastric cancer in nude mice were tested by pharmacodynamic and pathomorphology methods respectively. Results Comparing with NS, the L-OHP, CIK cells, and L-OHP ＋ CIK cells extended the survival time, decreased the abdomen circumference, and exfinoted the ascites of the mice （ P 〈 0.01）. The efficacy of L-OHP ＋ CIK was better than that of L-OHP and CIK cells （ P 〈 0.01）. Meanwhile, L-OHP group showed apoptosis of tumor cells and CIK group showed more marked tissue necrosis. In the combined therapy group, L- OHP ＋ CIK cells showed synergistic action on the mice. Conclusion The efficacy of L-OHP ＋ CIK cells is better than that of L-OHP or CIK cells alone in inhibiting growth of transplantable peritoneal metastasis of human gastric cancer in nude mice.