氧化应激促进大肠癌发展

Oxidative stress improve the progression of colon cancer

目的:探讨氧化应激对结肠癌细胞的影响及其在肿瘤发展中的作用。方法:将裸鼠分为4组,经腹腔内接种结肠癌细胞SW1116后,使用不同的药物处理:第1组:0.9%NaCl;第2组:0.9%NaCl+rhuMAb-VEGF;第3组:0.9%NaCl+H2O2;第4组:0.9%NaCl+H2O2+rhuMAb-VEGF;均于第1天,第3天/周腹腔注射,共6周。6周后处死动物,观察腹腔内肿瘤生长及腹水情况,对肿瘤组织中H2O2、VEGF及微血管密度检测。结果:与第1组相比,加入H2O2的第3组裸鼠,大部分动物(9/10)的腹腔内,包括大网膜、肠系膜上,布满明显增多大小不一的白色肿瘤结节,伴有大量腹水形成及肝、脾、胰腺转移;肿瘤组织中H2O2、VEGF明显增高,微血管密度增大;经rhuMAb-VEGF处理后,第2组与第1组相比肿瘤生长情况及腹水形成情况差异无统计学意义,第4组与第3组相比肿瘤生长及腹水形成情况明显减少,腹水及肿瘤、瘤周组织中H2O2、VEGF明显降低,微血管密度变小。结论:H2O2模拟的氧化应激可促进结肠癌细胞的生长和浸润,在大肠肿瘤的发展中具有促进作用,H2O2促进VEGF表达增加是其作用的机制之一。抗VEGF有望成为大肠癌的辅助治疗方法。

Objective： To study the contribution of oxidative stress in human colon cancer cells and the role in tumor dissemination. Methods： The four different nude mice groups with 0.9% NaCl d1,d3/wx6w,0.9%NaCl＋rhuMAb-VEGF d1,d3/wx6w,0.9%NaCl＋ H2O2 dl,d3/wx6w and 0.9% NaCl ＋ H2OE＋rhuMAb-VEGF dl,d3/wx6w respectively were treated after all the mice were treated with SWl116 cells in peritoneal cavity by i.p. injection. Six weeks later, the test animals were executed after etherization and then the formation of peritoneal dissemination and the capacity of malignant ascites, were observed and the amount of H2O2 with H2O2 kit, the VEGF level with Western blot and immunoinflurence, and the MVD （ microvessel dessity） in tumour tissue in different groups were confirmed. Results： H2O2 i.p. injection led more extensive tumor dissemination in the peritoneal cavity （more white tumor nodus in omentum and superior mesenteric） together with much ascites and more metastases at lever, spleen and pancreas. After injection with rhuMAb-VEGF, in the second group there was no differencs in the growth of tumor nodus and formation of ascites with the first group; the tumor nodus, the a mount of ascites and H2O2,and the MVD and the VEGF level are significantly lower in the forth group compared with the third group. Conclusion： Oxidative stress, mediated by hydrogen peroxide, can improve the growth and invasion of human colon cancer and make a potent role in tumor dissemination. One of the mechanisms is that hydrogen peroxide can improve VEGF expression in colon cancer. Anti-VEGF could be an adjunctive therapy in the treatment of colon cancer.