罗格列酮对人胃癌细胞侵袭转移的影响及其机制-消化内科专业毕业论文.docxVIP

PAGE PAGE 10 A组、B组、F组TIMP-3蛋白表达最少，C组、D组与A组、B组和F组比较差异有显著 性(P0.05)，E组表达最强。 结论： 1. 罗格列酮在体外能显著抑制SGC7901、SGC7901/VCR细胞迁移侵袭能力； 2. 罗格列酮抑制胃癌侵袭可能的机制是通过ERK/Fra-1通路在人胃癌SGC7901、 SGC7901/VCR细胞中及体内SGC7901/VCR细胞移植瘤中下调MMP-9、uPA的表达以 及上调TIMP-3的表达。 关键词：罗格列酮；人胃癌细胞；侵袭 Effects of Rosiglitazone on invasion and metastasis of gastric cancer cells and its mechanism ABSTRCT Objectives The study was undertaken to explore the effects of Rosiglitazone (ROS) on metastasis of human gastric cancer SGC7901 and SGC7901/VCR cell, and to explore the possible mechanisms. Methods The in vitro invasion assay was used to investigate the antimetastatic activities of ROS against SGC7901 and SGC7901/VCR cell. After treating SGC7901 and SGC7901/VCR cell with ROS(40μmol/L) for 24 hours, the transcription levels of uPA, uPAR, MMP-9 and TIMP-3 were assessed by reverse transcription-polymerase chain reaction(RT-PCR), and the protein levels of p-ERK1/ 2, Fra-1, uPA, uPAR, MMP-9 and TIMP-3 were assessed by western-blot. Immunohistochemistry detected the effects of Rosiglitazone on the protein expression of MMP-9, TIMP-3, uPA and uPAR in xenografted tumor of human gastric cancer SGC7901/VCR cell line on nude mice. Results The results of the in vitro invasion assay displayed that ROS was able to inhibit invasion ability of SGC7901 and SGC7901/VCR cells(P0.05). RT-PCR showed that treatment with 40μmol/L ROS for 24h extenuates the expression of uPA and MMP-9 mRNA(P0.05), increases the expression of TIMP-3 mRNA(P0.05), and has no effects on the expression of uPAR mRNA in SGC7901 and SGC7901/ VCR cells(P0.05). Western-blot showed that treatment with 40μmol/L ROS for 24h extenuates the protein levels of p-ERK1/ 2, Fra-1, uPA and MMP-9(P0.05), increases the protein levels of TIMP-3(P0.05), and has no effects on the expression of uPAR protein in SGC7901 and SGC7901/ VCR cells(P0.05). Immunohistochemistry shown that: the protein expression of MMP-9 was highest in group A and group B, there was significant difference among