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

Authors
 Soo Jung Gong  ;  Choon Jo Jin  ;  Hyun Cheol Chung  ;  Sun Young Rha 
Citation
 CANCER LETTERS, Vol.214(2) : 215-224, 2004 
Journal Title
 CANCER LETTERS 
ISSN
 0304-3835 
Issue Date
2004
MeSH
Antibiotics, Antineoplastic/pharmacology* ; Antibodies, Monoclonal/pharmacology* ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/pharmacology* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Cell Cycle/drug effects ; Cisplatin/pharmacology* ; Doxorubicin/pharmacology* ; Humans ; Immunohistochemistry ; Paclitaxel/pharmacology* ; Receptor, ErbB-2/analysis ; Receptor, ErbB-2/biosynthesis* ; Stomach Neoplasms/pathology* ; Trastuzumab ; Tumor Cells, Cultured
Keywords
Trastuzumab ; Chemotherapeutics ; Cytotoxicity ; Gastric cancer cell line
Abstract
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0304383504002757
DOI
10.1016/j.canlet.2004.04.029
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/111645
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