生长抑素受体基因对胰腺癌细胞侵袭转移影响的研究  

Anti-migratory and anti-invasive effect of somatostatin receptor type2 gene in human pancreatic carcinoma cell

作　　者：冯延平[1] 高军[1] 黄涛[1] 常青[1] 秦仁义[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院胆胰外科,湖北武汉430030

出　　处：《中国普通外科杂志》2005年第11期804-808,共5页China Journal of General Surgery

基　　金：国家自然科学基金资助项目(30271473)

摘　　要：目的探讨腺病毒介导的生长抑素受体2(SSTR 2)基因对胰腺癌BXPC-3细胞浸润、转移的抑制作用及其机制。方法利用腺病毒载体Adv-GFP-SSTR 2将人类SSTR 2全长cDNA转染导入胰腺癌细胞株BXPC-3,用RT-PCR及W esten-blot检测SSTR 2在mRNA水平及蛋白水平上的表达。利用Transwell小室测定转染SSTR 2前、后及转染空载体后细胞的穿膜侵袭运动能力;RT-PCR检测转染SSTR 2前后及转染空载体细胞的MMP-2和TIMP-2的表达。结果Adv-GFP-SSTR 2腺病毒转染胰腺癌BXPC-3后,可以稳定表达SSTR 2;细胞计数示转染后胰腺癌细胞穿透基底膜的数量较转染前明显减少(P<0.0 1),细胞侵袭力明显减弱;MMP-2转染后较转染前表达明显上调(P<0.0 1)、TIMP-2表达明显下调(P<0.0 1),MMP-2/TIMP-2比例下降。结论转染SSTR 2可明显抑制胰腺癌细胞的侵袭转移,其可能的机制是通过改变MMP-2/TIMP-2的比例而抑制肿瘤细胞对细胞外基质的降解。Objective To investigate the anti- migratory and anti- invasive effect of somatostatin receptor type 2 （SSTR2） gene transfection mediated by adenovirus in human pancreatic carcinoma cell and the mechanisms involved in this effect. Methods The full length human SSTR2 cDNA was introduced into pancreatic cancer cell line BXPC-3 by adenovirus-mediated transfection, and stable expression of RNA and protein of SSTR2 were detected by RT-PCR and Westen-blot. The Matrigel coated Transwell was used to detect the migratory and invasive ability of SSTR2-expressing cells, Adv-GFP control cells and mock control cells. Furthermore, the expressions of matrix metalloproteinase-2 （ MMP-2 ） and tissue inhibitor of metalloproteinase-2 （ TIMP-2 ） were detected by RT-PCR method in these ceils. Results The stable expression of SSTR2 was detected in BXPC-3 cells transfected by Adv-GFP-SSTR2. A dramatic decrease of BXPC-3 expressing SSTR2 cell migrated through a Matrigel-coated filter was observed, as compared with Adv-GFP control cells and mock control cells （ P 〈 0. 01 ）. Moreover, expressions of MMP-2 mRNA were significantly increased in the SSTR2-expressing cells and conversely the expressions of TIMP-2 mRNA were significantly reduced in the SSTR2-expressing cells compared with the Adv-GFP control and mock control （ P 〈0.01 ）. Conclusions The expression of reintroduced human SSTR2 gene in BXPC-3 cell by Adv-GFP-SSTR2 exerts mankedly anti-migratory and anti-invasive effect on pancreatic cancer cells, and the mechanisms involved in this effect may be by atteration of the MMP-2/TMP-2 ratio and thus suppress the degradation of extracellular matrix by cancer cells.

关 键 词：胰腺肿瘤/病理学 肿瘤浸润 受体 生长抑素 

分 类 号：R735.9[医药卫生—肿瘤] R392.11[医药卫生—临床医学]