Anti-tumor Effects of Growth Factor Inhibitors and Anti-metastatic Agents in Human Gastric Cancer Cell Lines.
- Author:
Sun Young RHA
1
;
Hee Cheol CHUNG
;
Soo Jung GONG
;
Hyun Cheol CHUNG
;
Joo Hang KIM
;
Jae Kyung ROH
;
Jin Sik MIN
;
Byung Soo KIM
Author Information
1. Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Gastric cancer;
Biological therapy;
Chemo-sensitization effect
- MeSH:
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
- From:Journal of the Korean Cancer Association
1997;29(3):391-403
- CountryRepublic of Korea
- Language:Korean
-
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.
