大肠癌细胞增殖中HGF/SF作用的观察
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李宏武

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The function of HGF/SF in the proliferation of colorectal cancer cells
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    目的:研究肝细胞生长因子/离散因子(HGF/SF)在诱导大肠癌细胞增殖中的作用。方法:采用Western Blot方法,检测HGF的受体c-met在受检大肠癌细胞株Caco-2,Colo320中的表达;观察Caco-2,Colo320中HGF/SF活化p42/p44MAPK和 p38MAPK的动态变化;应用[3H]-TdR,MTT方法观察p42/p44MAPK和p38MAPK传导通路阻滞剂PD98059和SB203580对HGF/SF诱导的大肠癌细胞增殖的抑制作用。结果:(1)c-met在Caco-2和Colo320中有表达。(2)HGF/SF激活p42/p44MAPK,p38MAPK:20ng/mL的HGF/SF处理细胞,p42/p44MAPK磷酸化在10min达高峰(2.28±0.01);p38MAPK变化与之相似(2.25±0.01)。(3)HGF/SF诱导大肠癌细胞的DNA合成增加依赖于p42/p44MAPK的激活, 在24h时点分别以20ng/mlHGF/SF,不同浓度(1μmol/L,5μmol/L,10μmol/L)的PD98059和SB203580处理细胞,HGF/SF使胸腺啶吸收增加(P<0.01);PD98059以浓度依赖性抑制胸腺啶的吸收(P<0.01)。(4)HGF促进Caco-2细胞的增殖,而PD98059对这种增殖有抑制作用。结论:HGF激活大肠癌细胞Caco-2和Colo320中p42/p44MAPK和p38MAPK;p42/p44MAPK参与HGF/SF诱导的大肠癌细胞Caco-2有丝分裂;HGF促进大肠癌细胞Caco-2增殖;HGF/SF和p42/p44MAPK在大肠癌细胞中发挥作用可能有细胞选择性。

    Abstract:

    Abstract:Objective:To study the function of hepatocyte growth factor/scatter factor(HGF/SF) in the proliferation of colorectal cancer cells. Methods:The expression of c-met,the receptor of HGF, was detected in Caco-2 and Colo320 cell lines by Western blot. The activation of p42/p44MAPK and p38MAPK induced by HGF in these two cell lines was observed. Observation of the effect of the inhibitor of p42/p44MAPK(PD98059), p38MAPK(SB203580) on the inhibition of HGF-induced proliferation of Caco-2 and Colo320 cells were made by Using [3H]-TdR, MTT assay. Results:(1)Both cell lines expressed the c-met.(2)HGF activated p42/p44MAPK and p38MAPK, and 20ng/ml HGF treated cells showed maximum activity in both to be within 10min.(p42/p44MAPK,2.28±0.01;p38MAPK, 2.25±0.01). (3)HGF was found to significantly increase [3H] thymidine incorporation(P<0.01) , when cells were pretreated with inhibitors of p42/p44MAPK (PD98059) in different doses(1μmol/L,5μmol/L,10μmol/L) ,HGF-induced thymidine uptake was suppressed in a dose-dependent manner(P<0.01). (4)MTT assay found HGF enhanced the proliferation of Caco-2 ,however, PD98059 inhibited this proliferation.Conclusions:The results demonstrate that HGF activates MAPK in both colorectal carcinoma cell lines, and p42/p44MAPK take part in the mitosis of the Caco-2 cells, while HGF promotes the proliferation of Caco-2 cells. The function of HGF/SF and p42/p44MAPK in colorectal cancer cells may have cellular selection.

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李宏武,张趣,梁健.大肠癌细胞增殖中HGF/SF作用的观察[J].中国普通外科杂志,2006,15(2):8-115.
DOI:10.7659/j. issn.1005-6947.2006.02.008

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  • 在线发布日期: 2006-02-25