摘要
目的探讨N-去硫酸肝素对人胃癌转移和P-选择素表达的影响。方法用SGC-7901人胃癌组织原位移值SCID小鼠30只,分试验组20只和正常对照组10只。其中试验组建立胃癌转移模型。术后d 3开始,试验组动物分别静脉注射NS(NS组,10只),每次100μL,每周2次,共3 wk;或N-去硫酸肝素(肝素组,10只),剂量为10 mg.kg-1.d-1,每周2次,共3 wk。术后wk 6末,所有动物处死。取部分胃癌组织作荧光定量PCR检测。结果NS组肿瘤转移率为80%(8/10),肝素组转移率为20%(2/10)。荧光定量PCR测定显示,SCID小鼠伴有癌转移者其胃癌中P-选择素mRNA表达较不伴癌转移者明显增强;肝素组10只中7只P-选择素mRNA表达较低。此外,正常胃组织中P-选择素表达水平较低。NS组P-选择素mRNA表达较正常小鼠明显增强,肝素组P-选择素mRNA表达较NS组低,P<0.05。N-去硫酸肝素无明显出血等不良反应。结论P-选择素表达与胃癌转移密切相关,N-去硫酸肝素对胃癌具有抗转移作用。
AIM To study the effect of N-desulfated heparin on metastasis, and P-selectin mRNA expression of human gastric carcinoma. METHODS SCID mice were implanted orthotopically using SGC-7901 human stomach carcinoma intact tissue. Mice were randomly divided into 2 groups which included NS gruop (normal saline) and NNH group (N-desulfated hepafin). Three days after treatment, animals received i.v. injections of normal saline or N-desulfated heparin( 10 mg· kg^-1·d^-1) twice weekly for 3 wk. Six weeks after operation all animals were sacrificed. Real time PCR technique was used to detect P-selectin mRNA expession. RESULTS Eight of the animals ( n = 10) treated with normal saline developed metastatic tumors in the regional lymph nodes, liver and lung.Two of the animals (n = 10) treated with N-desulfated heparin developed metastatic tumors in the organs examined. The level of P-selectin mRNA expression determined by real time PCR in gastric ccrcinoma tissue of SCID mice with tumor metastasis was higher than that without such metastasis. P-selectin mRNA expression was inhibitid by N-desulfated heparin. P-selectin mRNA expression in gastric tissue of normal mice was low. CONCLUSION The expression of P-selectin mRNA expression is associated with tumot metastasis. N-desulfated heparin can inhibit the metastasis of gastric cancer through blocking interactions between tumor cells and endothelium, and inhibit P-selectin expression with no obvious anticoagulant activity.
出处
《中国临床药学杂志》
CAS
2006年第2期67-70,共4页
Chinese Journal of Clinical Pharmacy
基金
科研上海市卫生局科研基金资助课题(No.034045)