Modulation of biological phenotypes for tumor growth and metastasis by target-specific biological inhibitors in gastric cancer.

SunYoung Rha, S. H. Noh, T. S. Kim, N. C. Yoo, J. K. Roh, J. S. Min, B. S. Kim

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

For tumor progression, a cascade of linked sequential biological events is essential. We tried to test whether biological therapy can modulate specific biological phenotypes and increase the anti-tumor effect when combined with chemotherapy. Five human gastric cancer cell lines (YCC-1, YCC-2, YCC-3, YCC-7, AGS) were used in these studies. Pentosan polysulfate (PPS) as a heparin-binding growth factor inhibitor, Tranexamic acid as a plasmin inhibitor, Lovastatin as an adhesion inhibitor and Adriamycin as a chemotherapeutic agent were selected. The effects of each drug on colony formation and tumor cell proliferation were evaluated by soft agar assay and cell proliferation assay, respectively to test direct anti-tumor effect. The expression of uPA, PAI-1 was determined by ELISA, while MMPs activity was evaluated by zymography. PPS suppressed the colony-forming activity as much as Adriamycin did, but it showed only cytostatic effects in cell proliferation assay. Migration capacity using Boyden chamber assay was more closely correlated with adhesive capacity than uPA or MMP-2 expression. The motility inhibitory effect of Tranexamic acid was observed in the YCC-7 cell line, which expressed all the required biological phenotypes for migration. In AGS, with high cell motility and adhesiveness, the adhesion was inhibited by Lovastatin and most of the inhibitory effect was recovered by Mevalonate. When PPS was combined with Adriamycin on the Adriamycin-resistant, midkine (MK) gene expressing YCC-7 cell line, the growth inhibition rate increased up to 84%, while that for a single treatment of PPS or Adriamycin was 40% and 22%, respectively (p=0.001). When we combined Tranexamic acid and Adriamycin, we observed the synergistic effect in YCC-3 and YCC-7, while no combined effect was found in YCC-1. The combination of Lovastatin and Adriamycin did not show any combined effects in any of the cell lines. In conclusion, a synergistic anti-proliferative effect (chemo-sensitization) with combined chemo-biotherapy was found in cancer cells with specific biological target, MK. The anti-motility effect was the greatest when the gastric cancer cells expressed all the specific biological phenotypes.

Original languageEnglish
Pages (from-to)203-212
Number of pages10
JournalInternational Journal of Molecular Medicine
Volume4
Issue number2
Publication statusPublished - 1999 Aug 1

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Doxorubicin
Stomach Neoplasms
Pentosan Sulfuric Polyester
Neoplasm Metastasis
Phenotype
Tranexamic Acid
Lovastatin
Growth
Neoplasms
Cell Line
Biological Therapy
Cell Proliferation
Matrix Metalloproteinases
Adhesiveness
Mevalonic Acid
Growth Inhibitors
Antifibrinolytic Agents
Plasminogen Activator Inhibitor 1
Cytostatic Agents
Adhesives

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Rha, SunYoung ; Noh, S. H. ; Kim, T. S. ; Yoo, N. C. ; Roh, J. K. ; Min, J. S. ; Kim, B. S. / Modulation of biological phenotypes for tumor growth and metastasis by target-specific biological inhibitors in gastric cancer. In: International Journal of Molecular Medicine. 1999 ; Vol. 4, No. 2. pp. 203-212.
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abstract = "For tumor progression, a cascade of linked sequential biological events is essential. We tried to test whether biological therapy can modulate specific biological phenotypes and increase the anti-tumor effect when combined with chemotherapy. Five human gastric cancer cell lines (YCC-1, YCC-2, YCC-3, YCC-7, AGS) were used in these studies. Pentosan polysulfate (PPS) as a heparin-binding growth factor inhibitor, Tranexamic acid as a plasmin inhibitor, Lovastatin as an adhesion inhibitor and Adriamycin as a chemotherapeutic agent were selected. The effects of each drug on colony formation and tumor cell proliferation were evaluated by soft agar assay and cell proliferation assay, respectively to test direct anti-tumor effect. The expression of uPA, PAI-1 was determined by ELISA, while MMPs activity was evaluated by zymography. PPS suppressed the colony-forming activity as much as Adriamycin did, but it showed only cytostatic effects in cell proliferation assay. Migration capacity using Boyden chamber assay was more closely correlated with adhesive capacity than uPA or MMP-2 expression. The motility inhibitory effect of Tranexamic acid was observed in the YCC-7 cell line, which expressed all the required biological phenotypes for migration. In AGS, with high cell motility and adhesiveness, the adhesion was inhibited by Lovastatin and most of the inhibitory effect was recovered by Mevalonate. When PPS was combined with Adriamycin on the Adriamycin-resistant, midkine (MK) gene expressing YCC-7 cell line, the growth inhibition rate increased up to 84{\%}, while that for a single treatment of PPS or Adriamycin was 40{\%} and 22{\%}, respectively (p=0.001). When we combined Tranexamic acid and Adriamycin, we observed the synergistic effect in YCC-3 and YCC-7, while no combined effect was found in YCC-1. The combination of Lovastatin and Adriamycin did not show any combined effects in any of the cell lines. In conclusion, a synergistic anti-proliferative effect (chemo-sensitization) with combined chemo-biotherapy was found in cancer cells with specific biological target, MK. The anti-motility effect was the greatest when the gastric cancer cells expressed all the specific biological phenotypes.",
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Modulation of biological phenotypes for tumor growth and metastasis by target-specific biological inhibitors in gastric cancer. / Rha, SunYoung; Noh, S. H.; Kim, T. S.; Yoo, N. C.; Roh, J. K.; Min, J. S.; Kim, B. S.

In: International Journal of Molecular Medicine, Vol. 4, No. 2, 01.08.1999, p. 203-212.

Research output: Contribution to journalArticle

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T1 - Modulation of biological phenotypes for tumor growth and metastasis by target-specific biological inhibitors in gastric cancer.

AU - Rha, SunYoung

AU - Noh, S. H.

AU - Kim, T. S.

AU - Yoo, N. C.

AU - Roh, J. K.

AU - Min, J. S.

AU - Kim, B. S.

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