TGFα-PE40对人低分化胃癌细胞生长的抑制作用

doi:10.3971/j.issn.1000-8578.1029

TGFα-PE40对人低分化胃癌细胞生长的抑制作用

Inhibitory Effect of TGFα-PE40 on the Growth of Human Poorly Differentiated Gastric Carcinoma Cells

摘要

摘要: 目的　探讨基因重组转化生长因子α-绿脓杆菌外毒素融合蛋白(TGFα-PE40，简称TP40)对人低分化胃癌细胞生长的导向抑制作用。方法　用免疫组化LSAB法检测人低分化胃癌MKN-45细胞表皮生长因子受体(EGFR)的表达，用结晶柴染色法和3H-亮氨酸掺入法检测TP40对MNK-45细胞生长及蛋白质合成的抑制，用过量EGF竞争拮抗TP40的细胞毒作用。结果　MKN-45细胞免疫组化显示出大量棕黄色的EGFR阳性染色。TP40浓度为1～100ng/ml时，对MKN-45细胞长生及蛋白质合成呈剂量依赖性抑制。过量EGF能完全拮抗TP40的细胞毒作用。结论　人低分化胃癌MKN-45细胞能高水平地表达EGFR，重组TP40对MKN-45细胞生长具有较强的抑制作用，作用部位为细胞的EGFR。

Abstract: Objective To investigate inhibitory effect of recombinant transforming growth factor α-Pseudomonas exotoxin fusion protein (TGFα-PE40;TP40) on the growth of cultured human poorly differentiated gastric carcinoma cells. Methods Expression of epidermal growth factor receptor (EGFR) in MKN-45 cells,a human poorly differentiated gastric carcinoma,was analyzed with immunohistochemistry.Inhibitory effects of TP40 on the growth of MKN-45 cells and cellular protein synthesis were analyzed with crystal violet staining and 3H-leucine incorporation.Competitive assays were performed by the over addition of EGF. Results The MKN-45 cells exhibited large amounts of brown immunoperoxidase reaction indicative of EGFR.When the concentration of TP40 was in the range of 1～100 ng/ml,TP40 inhibited the growth of MKN-45 cells and cellular protein synthesis in a dose-dependent form.Excess EGF completely blocked inhibitory effects of TP40. Conclusion The human poorly differentiated gastric carcinoma MKN-45 cells can express EGFR at high level.TP40 can significantly inhibit the growth of MKN-45 cells.The cytotoxic effects of TP40 were specifically mediated by EGFR.

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