Direct growth suppressive activity of interferon-alpha and -gamma on human gastric cancer cells.
OBJECTIVE
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.
Shyu
R Y
RY
Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan, Republic of China. jsy@ndmctsgh.edu.tw
Su
H L
HL
Yu
J C
JC
Jiang
S Y
SY
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013274:Stomach Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D016898:Interferon-alpha; D019253:Proto-Oncogene Proteins c-bcl-2; D007371:Interferon-gamma