热休克蛋白70在家族性腺瘤性息肉病中的表达及意义

Expression and Significance of Heat Shock Protein 70 in Familial Adenomatous Polyposis

目的研究热休克蛋白70(heat shock protein 70,HSP70)在小鼠家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)发生、发展中的表达及意义。方法采集1~16周Apc^Δ716/+小鼠肠道标本,通过体视显微镜观察、HE染色、免疫组织化学染色、蛋白质免疫印迹分析及RT-PCR等实验方法明确各周龄小鼠肠道息肉发生、发展及息肉内HSP70的表达情况。结果4周龄小鼠肠道开始出现息肉,息肉内HSP70表达仅轻度升高;8周龄小鼠肠道息肉快速增大,部分息肉开始出现癌变,息肉癌变组织内HSP70相对表达量及mRNA相对值与4周比较均显著升高,P均=0.000;12周龄小鼠肠道发生癌变的息肉明显增多,免疫组化染色息肉癌变组织HSP70相对表达量明显升高(与4周比较,P=0.000;与8周比较,P=0.063),HSP70的mRNA也显著升高(与4周比较,P=0.000,与8周比较,P=0.079)。结论Apc^Δ716/+小鼠肠道息肉开始形成时HSP70表达轻度升高,息肉癌变时HSP70显著升高,并维持高水平表达直至死亡,提示HSP70在Apc^Δ716/+小鼠肠道息肉开始形成时作用不显著,但在FAP息肉癌变及肠癌发展过程中有明显作用。该发现为HSP70应用于抑制FAP息肉癌变、延缓结直肠癌发展及结直肠癌免疫治疗等方面提供重要的理论依据。

Objective To investigate the expression and significance of Heat shock protein 70(HSP70)in familial adenomatous polyposis(FAP)mice.Methods The intestinal specimens of Apc^Δ716/+mice were collected at different ages of 1-16 weeks.The occurrence and development of polyps,as well as the expression of HSP70 in intestinal polyps were determined by means of stereo microscope,HE staining,immunohistochemical staining,Western blot and RT-PCR.Results The intestinal polyps occurred at 4 weeks,and the expression of HSP70 in polyps increased slightly.The intestinal polyps in mice aged 8 weeks increased rapidly,some polyps became cancerous,the expression of HSP70 and mRNA relative value in cancerous polyps increased significantly(P=0.000 compared with 4 weeks).Some intestinal polyps in 12-week-old mice were cancerous,and the expression of HSP70 in cancerous polyps of 12-week-old mice increased significantly(P=0.000 compared with 4 weeks,and P=0.063 compared with 8 weeks).The mRNA of HSP70 increased significantly(P=0.000 compared with 4 weeks,and P=0.079 compared with 8 weeks).Conclusion The expression of HSP70 increased slightly when the intestinal polyp of FAP mice began to form,but the expression of HSP70 increased significantly when the polyp became cancerous,and maintained at high level until death.These results showed that HSP70 had not such significant effect on the formation of polyps in FAP mice,but it had an obvious effect on the carcinogenesis of FAP polyp and the development of colorectal cancer.These findings provide an important theoretical basis for the application of HSP70 to FAP in the suppression of carcinogenesis of polyps and immunotherapy of colorectal cancer.