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

Authors
 SUN YOUNG RHA  ;  SUNG HOON NOH  ;  ÏAE SOO KIM  ;  NAE CHOON YOOU  ;  JAE KYUNG ROH  ;  JIN SIK MIN  ;  BYUNG SOO KIM  ;  MIN YOUNG KIM  ;  HYUN CHEOL CHUNG 
Citation
 International Journal of Molecular Medicine, Vol.4(2) : 203-212, 1999 
Journal Title
 International Journal of Molecular Medicine 
ISSN
 1107-3756 
Issue Date
1999
MeSH
Anticoagulants/pharmacology* ; Antineoplastic Agents/pharmacology ; Carrier Proteins/drug effects* ; Carrier Proteins/metabolism ; Cell Adhesion/drug effects ; Cell Division/drug effects* ; Cell Division/genetics ; Cell Movement/drug effects ; Cytokines* ; Doxorubicin/pharmacology ; Drug Synergism ; Gelatinases/antagonists & inhibitors ; Gelatinases/metabolism ; Humans ; Lovastatin/pharmacology ; Matrix Metalloproteinase 2 ; Metalloendopeptidases/antagonists & inhibitors ; Metalloendopeptidases/metabolism ; Mevalonic Acid/pharmacology ; Midkine ; Neoplasm Metastasis/prevention & control* ; Pentosan Sulfuric Polyester/pharmacology* ; Peptide Hydrolases/metabolism ; Phenotype ; Plasminogen Activator Inhibitor 1/metabolism ; Protease Inhibitors/pharmacology ; Stomach Neoplasms/drug therapy* ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology ; Tissue Inhibitor of Metalloproteinase-2/pharmacology ; Tumor Cells, Cultured ; Urokinase-Type Plasminogen Activator/metabolism
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.
Full Text
https://www.spandidos-publications.com/ijmm/4/2/203
DOI
10.3892/ijmm.4.2.203
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Noh, Sung Hoon(노성훈) ORCID logo https://orcid.org/0000-0003-4386-6886
Roh, Jae Kyung(노재경)
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/172919
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