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: The ET-A blockade by YM598 had a strong inhibitory effect against tumor growth and liver metastasis of the gastric cancer cell lines. These data suggest that YM598 has potential as a novel therapeutic agent for inhibiting liver metastasis of gastric cancer.
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 humangastric 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: The ET-A blockade by YM598 had a strong inhibitory effect against tumor growth and liver metastasis of the gastric cancer cell lines. These data suggest that YM598 has potential as a novel therapeutic agent for inhibiting liver metastasis of gastric cancer.
Authors: Pia Wülfing; Martin Götte; Barbara Sonntag; Christian Kersting; Hartmut Schmidt; Christian Wülfing; Horst Buerger; Robert Greb; Werner Böcker; Ludwig Kiesel Journal: Int J Oncol Date: 2005-04 Impact factor: 5.650
Authors: M Kusuhara; K Yamaguchi; K Nagasaki; C Hayashi; A Suzaki; S Hori; S Handa; Y Nakamura; K Abe Journal: Cancer Res Date: 1990-06-01 Impact factor: 12.701
Authors: D Salani; V Di Castro; M R Nicotra; L Rosanò; R Tecce; A Venuti; P G Natali; A Bagnato Journal: Am J Pathol Date: 2000-11 Impact factor: 4.307
Authors: A Bagnato; D Salani; V Di Castro; J R Wu-Wong; R Tecce; M R Nicotra; A Venuti; P G Natali Journal: Cancer Res Date: 1999-02-01 Impact factor: 12.701
Authors: M Nakamuta; M Ohashi; S Tabata; Y Tanabe; K Goto; M Naruse; K Naruse; K Hiroshige; H Nawata Journal: Am J Gastroenterol Date: 1993-02 Impact factor: 10.864
Authors: H Nishimori; T Yasoshima; R Denno; T Shishido; F Hata; Y Okada; H Ura; K Yamaguchi; H Isomura; N Sato; K Hirata Journal: Jpn J Cancer Res Date: 2000-07