[STI571对食管癌细胞系CE - 48T和CE - 81T的体外杀伤作用]

[In vitro killing effects of STI571 on esophageal carcinoma cell lines CE-48T and CE-81T].

作者信息

Zhang Peng-Yuan, Li Bao-Jiang, Su Xiao-Dong, Wen Zhe-Sheng, Zhao Jin-Ming, Zhang Lan-Jun, Long Hao, Rong Tie-Hua

机构信息

State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, China.

出版信息

Ai Zheng. 2006 Apr;25(4):456-60.

PMID:16613680

Abstract

BACKGROUND & OBJECTIVE: Tyrosine kinase mediates cell proliferation and differentiation, and plays important roles in tumorigenesis and development of esophageal carcinoma. STI571 is a tyrosine kinase inhibitor of platelet-derived growth factor receptor beta (PDGFR-beta) which is overexpressed in esophageal carcinoma. This study was to explore the in vitro killing effects of STI571 on esophageal carcinoma cell lines CE-48T and CE-81T.

METHODS

The expression of PDGFR-alpha and PDGFR-beta in CE-48T and CE-81T cells was detected by Western blot. The killing effects of STI571 on CE-48T and CE-81T cells were evaluated by MTT assay. Cell apoptosis was analyzed by flow cytometry with Annexin V/PI labeling. The expression of p-PDGFR-beta was detected by Western blot before and after treatment of STI571.

RESULTS

CE-48T cells expressed PDGFR-beta, but did not express PDGFR-alpha; CE-81T cells did not express both PDGFR-alpha and PDGFR-beta. The 50% inhibitory concentration (IC50) of STI571 was significantly lower for CE-48T cells than for CE-81T cells [(8.32+/-1.50) micromol/L vs. (41.02+/-7.64) micromol/L, P=0.002]. When treated with 10 micromol/L STI571 for 12 h, the apoptosis rate of CE-48T cells was (52.43+/-5.30)%, but the apoptosis rate did not increase as the treatment time and concentration increased. After treatment of STI571, the expression of p-PDGFR-beta was inhibited in CE-48T cells, but didn't change in CE-81T cells.

CONCLUSIONS

STI-571 could induce the apoptosis of PDGFR-beta-positive esophageal carcinoma CE-48T cells. p-PDGFR-beta might be the target of STI571.

摘要

背景与目的

酪氨酸激酶介导细胞增殖与分化，在食管癌的发生发展中起重要作用。STI571是一种血小板衍生生长因子受体β（PDGFR-β）的酪氨酸激酶抑制剂，其在食管癌中过表达。本研究旨在探讨STI571对食管癌细胞系CE-48T和CE-81T的体外杀伤作用。

方法

采用蛋白质免疫印迹法检测CE-48T和CE-81T细胞中PDGFR-α和PDGFR-β的表达。采用MTT法评估STI571对CE-48T和CE-81T细胞的杀伤作用。采用Annexin V/PI标记的流式细胞术分析细胞凋亡情况。在STI571处理前后，采用蛋白质免疫印迹法检测p-PDGFR-β的表达。

结果

CE-48T细胞表达PDGFR-β，但不表达PDGFR-α；CE-81T细胞既不表达PDGFR-α也不表达PDGFR-β。STI571对CE-48T细胞的50%抑制浓度（IC50）显著低于CE-81T细胞[（8.32±1.50）μmol/L对（41.02±7.64）μmol/L，P = 0.002]。用10 μmol/L STI571处理12 h时，CE-48T细胞的凋亡率为（52.43±5.30）%，但凋亡率并未随处理时间和浓度的增加而升高。STI571处理后，CE-48T细胞中p-PDGFR-β的表达受到抑制，但CE-81T细胞中未发生变化。