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胃泌素及其受体拮抗剂对人胃癌细胞株MKN45增殖及HB-EGF表达的影响

Effects of Gastrin and Its Antagonist on Cell Proliferation and Expression of HB-EGF in Human Gastric Cancer Line MKN45

  • 摘要: 目的 探讨胃泌素-17及其受体拮抗剂丙谷胺对人胃癌细胞株MKN45增殖及肝素结合表皮生长因子样生长因子(HB-EGF)表达的影响。方法MTT法观察细胞增殖活力;Western blot测定肝素结合表皮生长因子样生长因子(HB-EGF)蛋白的表达。结果MTT结果显示胃泌素-17在10-6~10-9 mol/L时具有明显的促MKN45细胞增殖作用(P<0.05);丙谷胺在10-2~10-3 mol/L时显著抑制MKN45细胞增殖(P<0.05);胃泌素+丙谷胺组中,丙谷胺(10-2~10-3 mol/L)能阻断并抑制胃泌素对胃癌细胞MKN45的促增殖作用(P<0.05)。同时,Western blot结果显示胃癌细胞株MKN45中有HB-EGF蛋白的表达。胃泌素-17在10-6~10-9 mol/L时可显著增强MKN45细胞株中HB-EGF蛋白表达(P<0.05);丙谷胺(10-2~10-3 mol/L)能阻断并抑制G-17(10-8 mol/L)诱导的HB-EGF蛋白表达上调(P<0.05)。 结论胃泌素-17促进人胃癌细胞MKN45增殖,其受体拮抗剂丙谷胺能阻断这一促进作用。胃泌素受体拮抗剂丙谷胺能抑制人胃癌细胞MKN45增殖。胃癌细胞株MKN45中有HB-EGF蛋白的表达,胃泌素-17促进HB-EGF蛋白表达上调,其受体拮抗剂丙谷胺能阻断并抑制这一促进作用。

     

    Abstract: Objective To explore the effects of gastrin-17 and its antagonist PGL on cell proliferation and the expression of HB-EGF in human gastric cancer line MKN-45. Methods MKN45 cells were incubated in the medium with gastrin-17 (10-6~10-10 mol/L),proglumide(10-2~10-4 mol/L) or combination of two agents (10-8 mol/L gastrin-17 and 10-2~10-4 mol/L proglumide).Cell growth and proliferation of MKN45 were analyzed by MTT assay,and expression of HB-EGF by Western blot. Results MTT showed gastrin-17 significantly promoted cell proliferation at the concentration of 10-6~10-9 mol/L (P<0.05),PGL at the concentration of 10-2~10-3 mol/L significantly inhibited the proliferation of MKN45 cells (P<0.05).In the combination of two agents,PGL (10-2~10-3 mol/L) significantly inhibite the proliferation of MKN-45 cells induced by gastrin-17 (P<0.05).Meanwhile,MKN45 had the expression of HB-EGF protein which significantly up-regulated by Gastrin-17 at the concertration of 10-6~10-9 mol/L.In the combination of two agents,PGL (10-2~10-3 mol/L) significantly inhibited the expression of HB-EGF stimulated by gastrin-17(P<0.05). Conclusion Gastrin-17 could promote cell proliferation of MKN45 cells in human gastric cancer,which strongly down-regulated by its antagonist PGL.Gastrin-17 significantly promoted the expression of HB-EGF,contrastly and inhibited an antagonist PGL.

     

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