摘要
背景与目的:聚(腺苷二磷酸核糖)聚合酶[poly(adenosine 5′-diphosphate ribose)polymerase,PARP]抑制剂5-氨基异喹啉酮(5-aminoisoquinolinone,5-AIQ)在炎症中具重要作用,但在肿瘤中的作用尚不清楚。本研究初步探讨5-AIQ对大肠癌PARP活性抑制的生物学作用。方法:链霉生物素-过氧化物酶法(Streptavidin-Peroxidase,SP)免疫组化法和免疫荧光双标法用于检测人大肠癌组织聚(腺苷二磷酸核糖)[poly(adenosine 5′-diphosphate ribose),PAR],及其与P-选择素(P-selectin)、细胞间粘附分子(intercellular adhesion molecule-1,ICAM-1)的共表达,大肠癌切缘肠粘膜为对照。通过粘附实验观察5-AIQ对结肠癌HT-29细胞系与人脐静脉血管内皮细胞(human umbilical vein endothelial cells,HUVEC)粘附的影响;同时采用SP法观察5-AIQ对HT-29细胞PAR、P-selectin和ICAM-1表达的影响。结果:45例大肠癌组织中,PAR阳性率(77.8%,35/45)明显高于对照肠粘膜(10.0%,1/10)(P<0.05);其中伴转移者PAR阳性率(86.7%,26/30)高于不伴转移者(60.0%,9/15)。PAR阳性与P-selectin和ICAM-1表达相关。结肠癌HT-29细胞与HUVEC粘附实验显示,5-AIQ浓度为100、300、500μmol/L时,细胞粘附率分别为56.79%、46.31%和39.77%,明显低于对照组(未加5-AIQ者)(粘附率为100%)。经5-AIQ处理的HT-29细胞PAR、P-selectin和ICAM-1表达HSCOR得分分别为1.41±0.12、1.57±0.13和1.23±0.13,明显低于未经5-AIQ处理的HT-29细胞(HSCOR得分分别为2.61±0.10、2.73±0.16和2.30±0.12)(P<0.05)。结论:大肠癌组织内PARP活性增强。PARP抑制剂5-AIQ可抑制大肠癌HT-29细胞与HUVEC的粘附,并可抑制大肠癌HT-29细胞PAR、P-selectin和ICAM-1表达。
BACKGROUND ＆ OBJECTIVE. 5-Aminoisoquinolinone（5-AIQ）, a poly（adenosine 5＇-diphosphate ribose） polymerase （PARP） inhibitor, plays an important role in inflammation, but its role in tumors is unclear. This study was to investigate the biological role of 5-AIQ-induced PARP inhibition in colon carcinoma cell line HT-29. METHODS. The expression of poly （adenosine 5＇-diphosphate ribose） （PAR） and co-expression of PAR with P-selectin and intercellular adhesion molecule-1 （ICAM-1） in 45 specimens of colorectal carcinoma and 10 specimens of adjacent normal colorectal mucosa were detected by SP immunohistochemistry and double immunofluorescence staining. After treatment of 5-AIQ, the adhesion of colon carcinoma cell line HT-29 to human umbilical vein endothelial cells （HUVEC） was detected by adhesion experiment; the expression of PAR, P-selectin, and ICAM-1 in HT-29 cells was detected by SP immunohistochemistry. RESULTS. The positive rate of PAR was significantly higher in colorectal carcinoma than in control colorectal mucosa （77.8% vs.10.0%,P〈0.05）,and higher in colorectal carcinomas with metastasis than in colorectal carcinomas without metastasis （86.7% vs.60.0%）.PAR expression was correlated to P-selectin and ICAM-1 expression. Cell adhesion rate was significantly lower in 100, 300, and 500 μmol/L 5-AIQ-treated HT-29 cells than in control cells （55.79%, 46.31%, and 39.77% vs. 100%, P〈0.05）. The protein levels of PAR, P-selectin, and ICAM-1 were significantly lower in 5-AIQ-treated HT-29 cells than in control cells （1.41±0.12 vs. 2.61±0.10, 1.57±0.13 vs. 2.73±0.16, 1.23±0.13 vs. 2.30±0.12, P〈0.05）. CONCLUSIONS：PARP activity is enhanced in colorectal carcinoma. PARP inhibitor 5-AIQ can inhibit the adhesion of HT-29 cells to HUVECs, and the expression of PAR, P-selectin, and ICAM-1 in HT-29 cells.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2007年第6期566-571,共6页
Chinese Journal of Cancer
基金
重庆市自然科学基金(No.CSTC2006BB5288)
重庆医科大学创新基金(No.CX200527)~~
