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表皮生长因子(EGF)受体特异性酪氨酸激酶抑制剂对胰腺癌细胞系的抑制作用比针对EGF和胰岛素样生长因子I(IGF I)受体的抑制性抗体更强。

The inhibitory effect of an EGF receptor-specific tyrosine kinase inhibitor on pancreatic cancer cell lines was more potent than inhibitory antibodies against the receptors for EGF and IGF I.

作者信息

Kobari M, Kullenberg B, Björkman A, Matsuno S, Ihse I, Axelson J

机构信息

Department of Surgery, University Hospital, Lund, Sweden.

出版信息

Int J Pancreatol. 1998 Oct;24(2):85-95. doi: 10.1007/BF02788565.

DOI:10.1007/BF02788565
PMID:9816541
Abstract

CONCLUSION

Epidermal growth factor (EGF) increased the cell number of the two pancreatic cancer cell lines, MiaPaCa-2 and LN-36, in vitro. A blockade of the EGF-R tyrosine kinase with tyrphostin was more efficient in reducing the cell number than inhibiting receptor antibodies. IGF-1 increased the cell number, and blockade of the IGF-1-R initially decreased the cell number that later was followed by an increase in LN-36.

BACKGROUND/AIM: The receptors and ligands of EGF and insulin-like growth factor-1 (IGF-1) are overexpressed in pancreatic cancer tissue. The aim of the present experiments was to study the effects of EGF and IGF-1 on the cell number in two pancreatic cancer cell lines.

MATERIAL AND METHODS

MiaPaCa-2 cells were grown in 0.2% fetal calf serum (FCS) and the newly established LN-36 cells in serum-free medium (SFM). The cell number was measured with the XTT method. The effects of EGF and IGF-1 were studied in combination with inhibiting receptor antibodies and an EGF-R-specific tyrosine kinase inhibitor, tyrphostin B56.

RESULTS

MiaPaCa-2 responded with increased cell number to stimulation with EGF, and at 10(-8) M or higher concentrations a dose-response pattern was seen. Administration of B56 to MiaPaCa-2 decreased the cell number by 87%. The inhibiting EGF-R-Ab only inhibited EGF-induced increase in cell number. IGF-1 doubled the cell number of MiaPaCa-2 and increased the cell growth induced by EGF. The inhibiting IGF-1-R-Ab reduced the cell number by 10%. The LN-36 cell line responded to EGF with an increased cell number with a maximum at 5 x 10(-9) M after 96 h. B56 reduced the cell number by 90% at 10(-5) M, with less effect during stimulation with EGF. In contrast to B56, the inhibiting EGF-R-Ab in the same experiment did not reduce the cell number. LN-36 responded to IGF-1 with an increased cell number, but EGF-stimulated growth was not influenced. The inhibiting IGF-1-R-Ab reduced the cell number and suppressed the IGF-1 stimulated increase after 24 h and later it induced an increased cell number.

摘要

结论

表皮生长因子(EGF)在体外增加了两种胰腺癌细胞系MiaPaCa - 2和LN - 36的细胞数量。用 tyrphostin阻断EGF - R酪氨酸激酶在减少细胞数量方面比抑制受体抗体更有效。胰岛素样生长因子-1(IGF - 1)增加了细胞数量,阻断IGF - 1 - R最初减少了细胞数量,随后LN - 36细胞数量增加。

背景/目的:EGF和胰岛素样生长因子-1(IGF - 1)的受体和配体在胰腺癌组织中过表达。本实验的目的是研究EGF和IGF - 1对两种胰腺癌细胞系细胞数量的影响。

材料与方法

MiaPaCa - 2细胞在0.2%胎牛血清(FCS)中培养,新建立的LN - 36细胞在无血清培养基(SFM)中培养。用XTT法测量细胞数量。研究了EGF和IGF - 1与抑制受体抗体及一种EGF - R特异性酪氨酸激酶抑制剂tyrphostin B56联合使用的效果。

结果

MiaPaCa - 2细胞对EGF刺激的反应是细胞数量增加,在10^(-8) M或更高浓度时呈现剂量反应模式。向MiaPaCa - 2细胞施用B56使细胞数量减少了87%。抑制性EGF - R抗体仅抑制EGF诱导的细胞数量增加。IGF - 1使MiaPaCa - 2细胞数量增加一倍,并增强了EGF诱导的细胞生长。抑制性IGF - 1 - R抗体使细胞数量减少了10%。LN - 36细胞系对EGF的反应是细胞数量增加,96小时后在5×10^(-9) M时达到最大值。10^(-5) M的B56使细胞数量减少了90%,在EGF刺激期间作用较小。与B56相反,同一实验中的抑制性EGF - R抗体并未减少细胞数量。LN - 36细胞对IGF - 1的反应是细胞数量增加,但EGF刺激的生长未受影响。抑制性IGF - 1 - R抗体减少了细胞数量,并在24小时后抑制了IGF - 1刺激的细胞数量增加,但随后又诱导细胞数量增加。

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