Abstract | BACKGROUND: With metastatic progression, gastric cancer is incurable. Using a DNA microarray, we performed differential gene expression analysis of established highly metastatic gastric cancer cell lines and compared the findings with those from a low-metastatic parental cell line. The results demonstrated that the endothelin A receptor (ET-A) gene was the only one from the highly metastatic cell lines that was generally up-regulated. METHODS: To investigate the role that ET-A plays in gastric cancer metastasis, we studied the effect of an ET-A-selective antagonist, YM598, on cell proliferation, tumor growth, and liver metastasis of the highly liver metastatic cell line AZ-H5c, established from the low metastatic human gastric cancer cell line AZ-521. RESULTS: An in vivo study using nude mice demonstrated that YM598 had a significant growth inhibition effect on AZ-H5c at doses of 0.5-10.0 mg/kg. The liver metastatic rate was also significantly reduced by YM598: control, 83.3%; 1 mg/kg dosage, 16.7%; 10 mg/kg, 20%; and pretreatment at 1 mg/kg, 16.7%. There was no evidence of gross toxicity resulting from the YM598 treatment. CONCLUSION:
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Authors | Rika Fukui, Hidefumi Nishimori, Fumitake Hata, Takahiro Yasoshima, Keisuke Ohno, Yoshiyuki Yanai, Kenjiro Kamiguchi, Ryuichi Denno, Noriyuki Sato, Koichi Hirata |
Journal | Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
(Gastric Cancer)
Vol. 10
Issue 2
Pg. 123-8
( 2007)
ISSN: 1436-3291 [Print] Japan |
PMID | 17577623
(Publication Type: Journal Article)
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Chemical References |
- Endothelin A Receptor Antagonists
- N-(6-methoxy-5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl)pyrimidin-4-yl)-2-phenylethenesulfonamide
- Pyrimidines
- RNA, Messenger
- Receptor, Endothelin A
- Sulfonamides
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Topics |
- Animals
- Cell Proliferation
(drug effects)
- Endothelin A Receptor Antagonists
- Female
- Flow Cytometry
- Humans
- Liver Neoplasms
(prevention & control, secondary)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Oligonucleotide Array Sequence Analysis
- Pyrimidines
(therapeutic use)
- RNA, Messenger
(genetics, metabolism)
- Receptor, Endothelin A
(genetics)
- Reverse Transcriptase Polymerase Chain Reaction
- Stomach Neoplasms
(drug therapy, pathology)
- Sulfonamides
(therapeutic use)
- Tumor Cells, Cultured
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