Growth inhibitory effects of trastuzumab and chemotherapeutic drugs in gastric cancer cell lines

被引：81

作者：

Gong, SJ

Jin, CJ

Rha, SY

Chung, HC

机构：

[1] Yonsei Univ, Coll Med, Ctr Canc, Canc Metastasis Res Ctr,Brain Korea Project Med S, Seoul 120752, South Korea

[2] Eulji Univ, Sch Med, Dept Internal Med, Seoul, South Korea

[3] Konkuk Univ, Coll Med, Dept Internal Med, Seoul, South Korea

来源：

CANCER LETTERS | 2004年 / 214卷 / 02期

关键词：

trastuzumab; chemotherapeutics; cytotoxicity; gastric cancer cell line;

D O I：

10.1016/j.canlet.2004.04.029

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The various treatments for advanced gastric cancer have limitations and induce only marginal survival benefit. HER-2/neu protein is overexpressed in several types of human cancers and its amplification is associated with poor prognosis. Recombinant humanized anti-HER-2/neu antibody (trastuzumab) not only inhibits the proliferation of HER-2/neu overexpressing tumor cells but also augments the cytotoxicity of concomitant chemotherapeutic agents in metastatic breast cancer. In this study, we evaluated the growth inhibitory effects of trastuzumab in gastric cancer cells. HER-2/neu protein was evaluated by immunohistochemical analysis in seven gastric cancer cell lines. MTT assay was performed to evaluate the growth inhibitory effects of trastuzumab and three chemotherapeutic agents, doxorubicin, cisplatin and paclitaxel, both alone and in combinations. The changes of cell cycle after trastuzumab treatment were analyzed by flow cytometry. Four of the cell lines, YCC-2 with strong positivity of HER-2/neu expression, NCI-N87 with moderate positivity, YCC-3 with weak positivity, and SK-BR-3 as a positive control, were selected. After in vitro MTT assay for 1-day and 5 consecutive days' treatment of trastuzumab at various concentrations, growth inhibition was not observed in any cancer cell lines. However, there was variable dose-dependent sensitivity to doxorubicin, cisplatin and paclitaxel. YCC-2 and SK-BR-3 cancer cells were more sensitive to three chemotherapeutic drugs, constantly (P<0.05). The combination of 5 consecutive days' treatment of trastuzumab with 1-day doxorubicin treatment showed significant growth inhibition only in YCC-2 and NCI-N87 gastric cancer cells. After 1-day trastuzumab treatment, the S-phase fraction was decreased by 52 and 70% in YCC-2 and SK-BR-3, respectively. In conclusion, the expressions of HER-2/neu protein in gastric cancer cells are variable, and concomitant treatments of trastuzumab with doxorubicin increase cytotoxicity. This suggests that trastuzumab-based biologic therapy with chemotherapeutic agents can be applied in gastric cancer treatment. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

引用

页码：215 / 224

页数：10

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