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两性调聚蛋白与晚期糖基化终产物对结肠癌细胞的不同作用。

Differential effects between amphoterin and advanced glycation end products on colon cancer cells.

作者信息

Kuniyasu Hiroki, Chihara Yoshitomo, Kondo Hideaki

机构信息

Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Japan.

出版信息

Int J Cancer. 2003 May 10;104(6):722-7. doi: 10.1002/ijc.11016.

Abstract

Amphoterin is 1 ligand of the receptor for advanced glycation end products (RAGE). We studied expression of amphoterin and RAGE mRNA and proteins in colorectal carcinoma cells and investigated their associations with the invasive activities of cells exposed to advanced glycation end products (AGE). Expression of RAGE and amphoterin was examined in 4 colorectal carcinoma cell lines. All cell lines expressed both RAGE and amphoterin. The effects of RAGE and amphoterin on cell growth (MTT assay), migration (wound healing assay) and invasion (in vitro invasion assay) were tested by treatment of cells with RAGE and amphoterin antisense S-oligodeoxynucleotides (ODNs). Cell growth, migration and invasion were inhibited significantly in Colo320 and WiDr carcinoma cells treated with RAGE and amphoterin antisense S-ODNs compared with sense-treated cells. Differences in ligand activity between amphoterin and AGE were examined with AGE-bovine serum albumin (BSA). AGE-BSA decreased cell growth, migration and invasion of amphoterin antisense S-ODN-treated Colo320 and WiDr cells compared with those of cells treated with Colo320 conditioned medium. Phosphorylation of extracellular signal-regulated kinase-1/2, Rac1 and AKT and production of matrix metalloproteinase 9 were increased to a greater degree by amphoterin than by AGE-BSA. In contrast, production of inducible nitric oxide synthase and nuclear factor-kappaBp65 were increased to a greater degree by AGE-BSA than by amphoterin.

摘要

双调蛋白是晚期糖基化终末产物受体(RAGE)的一种配体。我们研究了结直肠癌细胞中双调蛋白和RAGE的mRNA及蛋白表达,并探讨了它们与暴露于晚期糖基化终末产物(AGE)的细胞侵袭活性之间的关联。检测了4种结直肠癌细胞系中RAGE和双调蛋白的表达。所有细胞系均表达RAGE和双调蛋白。通过用RAGE和双调蛋白反义硫代寡脱氧核苷酸(ODN)处理细胞,测试了RAGE和双调蛋白对细胞生长(MTT法)、迁移(伤口愈合试验)和侵袭(体外侵袭试验)的影响。与正义链处理的细胞相比,用RAGE和双调蛋白反义硫代ODN处理的Colo320和WiDr癌细胞的细胞生长、迁移和侵袭受到显著抑制。用AGE-牛血清白蛋白(BSA)检测双调蛋白和AGE之间配体活性的差异。与用Colo320条件培养基处理的细胞相比,AGE-BSA降低了双调蛋白反义硫代ODN处理的Colo320和WiDr细胞的细胞生长、迁移和侵袭。与AGE-BSA相比,双调蛋白使细胞外信号调节激酶-1/2、Rac1和AKT的磷酸化以及基质金属蛋白酶9的产生增加得更多。相反,与双调蛋白相比,AGE-BSA使诱导型一氧化氮合酶和核因子-κBp65的产生增加得更多。

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