维甲酸对结直肠癌组织维甲酸受体和增殖细胞核抗原表达的影响

Effect of retinoic acid on retinoic acid receptor and proliferating cell nuclear antigen in colorectal cancer

目的探讨维甲酸(RA)对结直肠癌组织维甲酸受体(RAR)和增殖细胞核抗原(PCNA)表达的影响。方法选Wistar大鼠160只,随机分4组。第1、2组注射二甲基肼,第3、4组注射生理盐水。于第7周开始,第2、3组每天给大鼠灌服维甲酸50mg/kg,至第14周,然后分批处死。用受体放射性配基结合分析法测定正常结直肠组织和癌组织的RAR含量和用免疫组织化学法计算PCNA指数。结果第1、2组结直肠癌发生率100%和15%,差异有非常显著性意义(P<0.01)。注射RA前后正常结直肠组织和结直肠癌组织RAR水平分别为2.64、2.11、1.16和1.78fmol/μgDNA,RA可使癌组织RAR水平升高(P<0.01)。注射RA治疗前后正常结直肠组织和癌组织PCNA分别为33、33、168、98,RA能明显降低结直肠癌组织PCNA指数(P<0.01)。结论RA可以减少二甲基肼诱发结直肠癌的发生;并可使结直肠癌组织的RAR水平上升和PCNA水平下降。

Objective To investigate the effect of retinoic acid (RA) on retinoic acid receptor (RAR) and proliferating cell nuclear antigen (PCNA) in colorectal carcinoma.Methods 160 healthy male Wistar rats were divided into 4 groups. Rats in group 1 and 2 was induced by dimethylhydrazine (DMH)(20 mg/kg, once a week, injected subdermally) for 14 weeks; meanwhile group 3 and 4 were injected with normal saline. Rats in group 2 and 3 were treated with RA (50 mg/kg, every day, orally) from 7th to 14th week; group 4 was used as control. And then the rats were killed in different batch. The concentration of RAR and number of PCNA were examined in normal colorectal and carcinoma tissue. Results The incidence of colorectal carcinoma were different between group 1(100%) and 2(15%)(P< 0 05).Levels of RAR in normal and cancer group before and after RA treatment were 2 64,2 11,1 16,1 78 fmol/μg DNA respectively. PCNA indexes in normal and cancer group before and after RA treatment were 33, 33 and 168, 98(P< 0 05). Conclusions RA can decrease the incidence of colorectal carcinoma induced by DMH. Colorectal cancer tissue presents abnormal expression of RAR and PCNA. RA can inhibit the expression of PCNA and increase RAR concentration in colorectal cancer tissues.