PARP抑制剂对小鼠结肠腺癌CT26细胞肝转移的影响

Effect of poly (ADP-ribose) polymerase inhibitor on liver metastasis of colorectal carcinoma CT26 cell line in mice

目的探讨5-AIQ抑制小鼠结肠癌CT26细胞聚腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]后对其肝转移的影响。方法以小鼠脾脏接种小鼠结肠癌CT26细胞肝转移为模型,采用CT26细胞体外药物处理后脾脏接种和脾脏接种后直接腹腔给药两种方式,将36只BALB/c小鼠按随机区组设计分成6组,其中4组做实验组,2组做对照组,每组6只。观察脾脏原发肿瘤和肝脏转移肿瘤的变化。Western blot检测PARP在各组脾脏原发瘤组织中的蛋白表达量。结果经过药物5-AIQ处理后,CT26细胞脾脏接种的小鼠和CT26细胞直接脾脏接种后腹腔给药处理的小鼠,脾脏肿瘤体积缩小和肝脏转移结节数目及分级减少,与对照组比较差别显著(P<0.05),但是不同剂量之间未见明显差异(P>0.05)。各5-AIQ处理组小鼠脾脏组织PARP表达明显低于未给药处理小鼠脾脏原发瘤组织(P<0.05)。结论5-AIQ能抑制CT26细胞PARP表达,对结肠癌CT26细胞脾脏原发瘤的生长及肝转移具有一定的抑制作用。

Objective To investigate the effect of poly （ADP-ribose） polymerase （PARP hibited by 5-AIQ on the liver metastasis in colorectal carcinoma CT26 cell lines. Methods ） expression in- Liver metastasis model of colorectal carcinoma was established by intrasplenic inoculation of colorectal carcinoma CT26 cell in BALB/c mice. Treated by 5-AIQ （ 100 or 500 μmol/L） , CT26 cells were inoculated to the spleen of the mice, or the rats were first inoculated of CT26 cells, then treated by 5-AIQ （3 or 10 mg/kg） ip. The changes spleen primary carcinoma and liver metastasis carcinoma were observed. The PARP expression in spleen primary carci- noma was detected by Western blotting. Results Significant difference was found in the splenic carcinoma size, the number of liver metastatic nodules, the grading of liver metastatic nodules in the 5-AIQ treated group and control group （P 〈 0.05 ） , but no statistical significance was observed in the mice treated with different drug dosages （P 〉 0. 05 ）. The PARP expression of spleen primary carcinoma in 5-AIQ treated groups was lower significantly than that in control group （P 〈0.05）. Conclusion 5-AIQ can inhibit PARP expression in the CT26 cell lines and the growth of primary splenic carcinoma and liver metastasis after CT26 cell inoculation in vivo.