SPARC对胃癌细胞系HGC27体内侵袭能力及MMP-2表达的影响

The Role of SPARC in the Invasion of Gastric Cancer in Vivo and I·s Relationship with Matrix Metalloproteinase-

目的:探讨短发夹shRNA干扰抑制富含半胱氨酸的酸性分泌蛋白(SPARC)表达对胃癌细胞体内侵袭能力的影响及其部分机制。方法:利用稳定转染SPARC shRNA的人类胃癌细胞系HGC 27、转染空白载体对照和未转染的HGC 27细胞分别接种在裸鼠皮下生成皮下种植瘤来观察胃癌细胞在体内的侵袭能力的变化。对获得的裸鼠种植瘤标本通过Western blot进行SPARC、基质金属蛋白酶MMP-2表达的检测及相关性分析。结果:与空载转染对照组和HGC 27细胞组比较,SPARC shRNA转染组的生长减慢,肿瘤缩小,并且侵袭的范围也明显减少(P<0.05)。同时,转染了SPARC shRNA的HGC 27细胞组的肿瘤SPARC表达水平降低(P<0.05);转染了SPARC shRNA的HGC 27细胞组的肿瘤MMP-2表达水平降低(P<0.05),且SPARC和MMP-2表达差异之间具有显著相关性(r=0.878,P<0.01)。结论:RNA干扰抑制SPARC可以降低胃癌细胞的体内生长和侵袭能力,其部分机制可能是抑制SPARC可以下调MMP-2的表达。

Objective： To investigate the role of SPARC shRNA in the growth and metastasis of human gastric cancer cells and in the regulation of MMP-2.Methods：The plasmids bearing SPARC shRNA were transfected into HGC 27 cells by the way of lipofactamine 2000. SPARC proteins in transfected cells were detected by Westem blot. Then the transfected and untransfected tumor cells were implanted into nude mice （Babl/c Nu/Nu）. In the prophasic study of our laboratory the HGC 27 cells transfected with SPARC shRNA and untransfected HGC 27 cells were implanted subcutaneously into nude mice （Babl/c Nu/Nu） respectively. In this study the expression of SPARC and MMP-2 in the tumors from the nude mice was tested by IHC and Western blot. Results：HGC 27 cells with SPARC shRNA transfection showed decreased SPARC expression compared with the cells without transfcction and control transfection. The expression of SPARC and MMP-2 of the tumors from SPARC shRNA transfected HGC 27 cells was less than that from untransfected HGC 27 cells. And there was significant correlation among them.Conelusions：SPARC shRNA can decrease the growth and metastatic ability of human gastric cancer cells in vivo, partly through downregulating the expression of MMP-2 in gastric cancer.