J Korean Cancer Assoc.  1997 Jun;29(3):391-403.

Anti-tumor Effects of Growth Factor Inhibitors and Anti-metastatic Agents in Human Gastric Cancer Cell Lines

• Rha SY
• Chung HC
• Gong SJ
• Chung HC
• Kim JH
• Roh JK
• Min JS
• Kim BS

Abstract

PURPOSE: For tumor growth, invasion and metastasis, a cascade of linked sequential biological events is essential; overproduction of growth factors, activation of proteolytic enzymes, induction of tumor angiogenesis, and enhanced tumor cell motility and attachment. We tried to test whether the biological therapy against the biological targets can modulate the specific biological characteristics, and furthermore increased anti-tumor effects can be induced when the biological therapy and cytotoxic chemotherapy were combined.
MATERIALS AND METHODS
YCC-1, 2, 3, 7, and AGS human gastric cancer cell lines were used in these studies. Pentosan polysulfate (PPS) as a heparin-binding growth factor (HBGF) inhibitor, Tranexamic acid as a plasmin inhibitor, Adriamycin as a chemotherapeutic agent, were selected. The methods were Northern blot analysis for the detection of Midkine (MK) expression, soft agar assay for autocrine tumorigenicity. The expression of uPA, PAI-1 was determined by ELISA, while the MMPs activities were evaluated by zymography. The effects of each drug on tumorigenicity and tumor cell proliferation were evaluated by soft agar assay and cell proliferation assay, respectively.
RESULTS
YCC-3, 7, AGS cell lines expressed MK mRNA, whereas YCC-1, 2 did not. YCC-2 cell line showed increased expression of uPA and MMP activities. Only MK expressing YCC-3 and 7 cell lines showed the tumorigenicity. PPS suppressed the colony forming activities as much as Adriamycin did (PPS; 8~24%, Adriamycin; 12~40%), but it showed only cytostatic effects in cell proliferation assay (PPS; 60~103%, Adriamycin; 22~97%). When PPS was combined with Adriamycin on the Adriamycin resistant, MK expressing YCC-7 cell line, the growth inhibition rate increased up to 84%, while that of PPS or Adriamycin single treatment was 40%, 22%, respectively (p=0.001).
CONCLUSION
The modulation of specific biological targets can induce the anti-tumor effects. This suggests the possible clinical application of biological therapy in gastric cancer.

Keyword

Gastric cancer; Biological therapy; Chemo-sensitization effect

MeSH Terms

Agar
Antifibrinolytic Agents
Biological Therapy
Blotting, Northern
Cell Line*
Cell Movement
Cell Proliferation
Doxorubicin
Drug Therapy
Enzyme-Linked Immunosorbent Assay
Humans*
Intercellular Signaling Peptides and Proteins
Matrix Metalloproteinases
Neoplasm Metastasis
Pentosan Sulfuric Polyester
Peptide Hydrolases
Plasminogen Activator Inhibitor 1
Population Characteristics
RNA, Messenger
Robenidine
Stomach Neoplasms*
Tranexamic Acid
Agar
Antifibrinolytic Agents
Doxorubicin
Intercellular Signaling Peptides and Proteins
Matrix Metalloproteinases
Pentosan Sulfuric Polyester
Peptide Hydrolases
Plasminogen Activator Inhibitor 1
RNA, Messenger
Robenidine
Tranexamic Acid