Correlation between HER-2/neu(erbB-2) expression level and therapeutic effect of combination treatment with HERCEPTIN and chemotherapeutic agents in gastric cancer cell lines.
BACKGROUND
Although advanced gastric cancer has many limitations and response rate is marginal in chemotherapy. Overexpression of human epidermal growth factor receptor 2(HER-2/neu) gene and its protein are associated with increased cell division and a high rate of tumor growth and have been reported in several malignancies. Especially, approximately 30% of breast cancer patients have overexpression of HER-2/neu protein and the overexpression metastasize faster, induces resistance of the chemotherapy and down-regulate function of estrogen receptor. Recombinant humanized anti-HER2 antibody (Herceptin) inhibits proliferation of HER-2/neu overexpressing tumor cells and the use of that in combination in metastatic breast cancer have increased cytotoxicity of chemotherapeutic agents.


METHODS
We evaluated the expression of HER-2/neu protein in gastric cell lines by FACS and then comparing the cytotoxicity in chemotherapeutics (doxorubicin, cisplatin, paclitaxel, 5-FU) alone and in combination with Herceptin according to the expression of HER-2/neu protein by MTT assay.


RESULTS
1. NCI-N87 (88%) gastric cancer cell line and SK-BR-3 (89%) breast cancer cell line with strong positivity of HER-2/neu expression. YBC-2 (55%) and YBC-3 (48%) gastric cancer cell line with intermediated, weak positivity respectively. Negative control U-87 MG (6%) brain cancer cell line were showed low expression of HER-2/neu. 2. Cell growth was dose-dependently inhibited in HER-2/neu positive, control cell line SK-BR-3 by Herceptin treatment but not observed in HER-2/neu negative control cell line U-87 MG. Effective growth inhibition was not observed in gastric cancer cell lines with single treatment of Herceptin, all cell lines observed the dose-dependent growth inhibition to chemotherapeutic agents (doxorubicin, cisplatin, paclitaxel and 5-FU). 3. Combination of Herceptin with doxorubicin observed synergistic effects in all cancer cell lines except YBC-3, combination of Herceptin with cisplatin observed NCI-N87 and SK-BR-3 and combination of Herceptin with paclitaxel observed synergistic effects in YBC-2. Combination of Herceptin with 5-FU observed antagonistic effects in all cancer cell lines.


CONCLUSIONS
According to HER-2/neu expression level, effect of anti-cancer agents was observed differently in combination of Herceptin with chemotherapeutic agents. This suggests that HER-2/neu expression level can be applied standard of combination drug selection in combination of Herceptin With chemotherapeutic agents in gastric cancer.
Department of Oncology, Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, People's Republic of China.
Hai
H
Cui
Jilin Cancer Hospital, Changchun, China.
Ying
Y
Cheng
Department of Oncology, Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, People's Republic of China.
Su-Zhou
SZ
Piao
Department of Pathology, Yanbian University, Yanji, China.
Yun-Jie
YJ
Xu
Department of Oncology, Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, People's Republic of China.
Hong-Hua
HH
Sun
Department of Oncology, Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, People's Republic of China.
Xian
X
Cui
Department of Oncology, Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, People's Republic of China.
Xiang-Zi
XZ
Li
Department of Oncology, Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, People's Republic of China.
Song-Nan
SN
Zhang
Department of Oncology, Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, People's Republic of China.
Long-Zhen
LZ
Piao
Department of Oncology, Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, People's Republic of China.
Yong-Min
YM
Jin
Department of Pathology, Yanbian University, Yanji, China.
Zhen-Hua
ZH
Lin
Department of Oncology, Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, People's Republic of China.
Xiong-Hu
XH
Shen