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Direct growth suppressive activity of interferon‐α and ‐γ on human gastric cancer cells
Author(s) -
Shyu RongYaun,
Su HuiLing,
Yu JyhCheng,
Jiang ShunYuan
Publication year - 2000
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/1096-9098(200010)75:2<122::aid-jso9>3.0.co;2-4
Subject(s) - apoptosis , cell cycle , dna fragmentation , flow cytometry , microbiology and biotechnology , cell growth , cell cycle checkpoint , growth inhibition , interferon gamma , cancer cell , biology , cancer research , cell , immune system , programmed cell death , immunology , cancer , biochemistry , genetics
Background and Objectives Interferons (IFNs) exhibit anti‐tumor activities through either immune modulation or direct anti‐tumor effects. We have investigated the activity and mechanisms of IFN‐α and IFN‐γ on the growth of TSGH9201, TMK‐1 and AGS gastric cancer cells in vitro. Methods Activities of IFNs on cell growth were analyzed by measuring total cellular DNA. Effects of IFNs on apoptosis was evaluated by formation of in situ DNA breakage and DNA ladders. Effects of IFNs on cells cycle phase distribution were analyzed using flow cytometry. Levels of Bcl‐2 family proteins after treatment with IFNs were analyzed using Western blot. Results Both IFN‐α and IFN‐γ were active in suppressing the growth of TSGH9201 and TMK‐1 cells, while AGS cells were resistant to treatment with IFNs. The IC 50 s of IFN‐α for TSGH9201 and TMK‐1 cells were 300 and 500 U/ml, respectively, and the IC 50 s of IFN‐γ were 40 and 2.0 U/ml, respectively. Both IFN‐α‐ and IFN‐γ‐induced cell cycle arrest in sensitive cells. IFN‐γ also increased cellular apoptosis, demonstrated by increasing in situ DNA damage and DNA fragmentation. IFN‐γ increased BAK protein levels and decreased Bcl‐2 and Bcl‐X S protein levels in TSGH9201 cells. Conclusions IFN‐α suppressed growth of gastric cancer cells through induction of cell cycle arrest. IFN‐γ suppressed cell growth through induction of both cell cycle arrest and apoptosis. IFN‐γ‐mediated apoptosis was associated with the alteration in protein levels of Bcl‐2, Bcl‐X S and BAK. J. Surg. Oncol. 2000:75:122–130. © 2000 Wiley‐Liss, Inc.