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Direct growth suppressive activity of interferon-alpha and -gamma on human gastric cancer cells
1Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan, Republic of China. jsy@ndmctsgh.edu.tw
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-alpha and IFN-gamma 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-alpha and IFN-gamma 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-alpha for TSGH9201 and TMK-1 cells were 300 and 500 U/ml, respectively, and the IC(50)s of IFN-gamma were 40 and 2.0 U/ml, respectively. Both IFN-alpha- and IFN-gamma-induced cell cycle arrest in sensitive cells. IFN-gamma also increased cellular apoptosis, demonstrated by increasing in situ DNA damage and DNA fragmentation. IFN-gamma increased BAK protein levels and decreased Bcl-2 and Bcl-X(S) protein levels in TSGH9201 cells.
Conclusions:
IFN-alpha suppressed growth of gastric cancer cells through induction of cell cycle arrest. IFN-gamma suppressed cell growth through induction of both cell cycle arrest and apoptosis. IFN-gamma-mediated apoptosis was associated with the alteration in protein levels of Bcl-2, Bcl-X(S) and BAK.
Insights
Interferons (IFNs) show anti-cancer effects. Both Interferon-alpha and Interferon-gamma suppressed gastric cancer cell growth, with Interferon-gamma also inducing apoptosis.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Interferons (IFNs) possess anti-tumor properties via immune modulation or direct effects.
- Gastric cancer cell lines (TSGH9201, TMK-1, AGS) were utilized to investigate IFN activity.
Purpose of the Study:
- To investigate the activity and mechanisms of Interferon-alpha (IFN-alpha) and Interferon-gamma (IFN-gamma) on gastric cancer cell growth.
- To determine the effects of IFNs on cell cycle progression and apoptosis in vitro.
Main Methods:
- Cell growth inhibition was assessed by measuring total cellular DNA.
- Apoptosis was evaluated using in situ DNA breakage and DNA ladder assays.
- Cell cycle phase distribution was analyzed via flow cytometry, and Bcl-2 family protein levels were determined by Western blot.
Main Results:
- IFN-alpha and IFN-gamma inhibited the growth of TSGH9201 and TMK-1 cells, with AGS cells showing resistance.
- Both IFNs induced cell cycle arrest in sensitive cells. IFN-gamma also promoted apoptosis and altered Bcl-2 family protein expression (increased BAK, decreased Bcl-2 and Bcl-X(S)).
Conclusions:
- IFN-alpha suppressed gastric cancer cell growth primarily through cell cycle arrest.
- IFN-gamma inhibited growth via cell cycle arrest and apoptosis, with the latter linked to changes in Bcl-2 family proteins.