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

Soo Jung Gong, Choon Jo Jin, SunYoung Rha, Hyuncheol Chung

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)215-224
Number of pages10
JournalCancer Letters
Volume214
Issue number2
DOIs
Publication statusPublished - 2004 Oct 28

Fingerprint

Stomach Neoplasms
Cell Line
Growth
Pharmaceutical Preparations
Doxorubicin
Therapeutics
Neoplasms
Trastuzumab
Biological Therapy
Proteins
S Phase
Cell Cycle
Flow Cytometry
Breast Neoplasms
Survival
Antibodies

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

@article{71905ae9c2b44de3948cc7721eca7fbd,
title = "Growth inhibitory effects of trastuzumab and chemotherapeutic drugs in gastric cancer cell lines",
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.",
author = "Gong, {Soo Jung} and Jin, {Choon Jo} and SunYoung Rha and Hyuncheol Chung",
year = "2004",
month = "10",
day = "28",
doi = "10.1016/j.canlet.2004.04.029",
language = "English",
volume = "214",
pages = "215--224",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

Growth inhibitory effects of trastuzumab and chemotherapeutic drugs in gastric cancer cell lines. / Gong, Soo Jung; Jin, Choon Jo; Rha, SunYoung; Chung, Hyuncheol.

In: Cancer Letters, Vol. 214, No. 2, 28.10.2004, p. 215-224.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Growth inhibitory effects of trastuzumab and chemotherapeutic drugs in gastric cancer cell lines

AU - Gong, Soo Jung

AU - Jin, Choon Jo

AU - Rha, SunYoung

AU - Chung, Hyuncheol

PY - 2004/10/28

Y1 - 2004/10/28

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=4444238149&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444238149&partnerID=8YFLogxK

U2 - 10.1016/j.canlet.2004.04.029

DO - 10.1016/j.canlet.2004.04.029

M3 - Article

C2 - 15363548

AN - SCOPUS:4444238149

VL - 214

SP - 215

EP - 224

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 2

ER -