酪氨酸激酶抑制剂AG490可抑制癌细胞生长，并在LS174T和HT-29细胞中激活细胞外信号调节激酶（ERK）。

The tyrosine kinase inhibitor AG490 inhibits growth of cancer cells and activates ERK in LS174T and HT-29 cells.

作者信息

Saito Koichi, Iwashita Jun, Murata Jun, Abe Tatsuya

机构信息

Molecular Biology Laboratory, Akita Prefectural University, Akita 010-0195, Japan.

出版信息

Anticancer Res. 2006 Mar-Apr;26(2A):1085-90.

PMID:16619510

Abstract

BACKGROUND

The activity of tyrosine kinases, although strictly regulated in normal cells, is often disturbed in cancer cells. The inhibition of a tyrosine kinase could be a target for treating cancer.

MATERIALS AND METHODS

The colon cancer cell lines LS174T and HT-29 and the lung cancer cell line NCI-H292 were used. The cells were incubated with 100 microM of the tyrosine kinase inhibitor AG490 for 1-3 days and were examined for growth. Extracellular signal-regulated kinase (ERK) activation was detected by anti-phospho ERK antibodies. The cell cycle was analyzed by flow cytometry.

RESULTS

AG490 inhibited the growth of LS174T, HT-29 and NCI-H292 cells without inducing apoptosis. Short-term treatment with AG490 activated ERK and p38 MAPK in the LS174T and HT-29 cells, but not in NCI-H292 cells. ERK activation, however, was unrelated to the growth inhibition in LS174T cells, because the inhibition persisted even after the prevention of ERK activation.

CONCLUSION

AG490 inhibits the growth of some cancer cells and activates ERK in LS174T and HT-29 cells. ERK activation is unrelated to growth inhibition.

摘要

背景

酪氨酸激酶的活性在正常细胞中虽受到严格调控，但在癌细胞中常被扰乱。抑制酪氨酸激酶可能成为治疗癌症的一个靶点。

材料与方法

使用结肠癌细胞系LS174T和HT - 29以及肺癌细胞系NCI - H292。将细胞与100微摩尔的酪氨酸激酶抑制剂AG490孵育1 - 3天，并检测其生长情况。通过抗磷酸化ERK抗体检测细胞外信号调节激酶（ERK）的激活情况。采用流式细胞术分析细胞周期。

结果

AG490抑制LS174T、HT - 29和NCI - H292细胞的生长，且不诱导细胞凋亡。短期用AG490处理可激活LS174T和HT - 29细胞中的ERK和p38丝裂原活化蛋白激酶（MAPK），但不激活NCI - H292细胞中的这些激酶。然而，ERK的激活与LS174T细胞的生长抑制无关，因为即使在阻止ERK激活后，抑制作用仍持续存在。