Direct growth suppressive activity of interferon-alpha and -gamma on humangastric cancer cells

Background and Objectives: Interferons (IFNs) exhibit anti-tumor activities through either immune modulation or direct anti-tumor effects. We have inv estigated the activity and mechanisms of IFN-alpha and IFN-gamma on the gro wth of TSGH9201, TMK-1 and ACTS 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 i n situ DNA breakage and DNA ladders. Effects of IFNs on cells cycle phase d istribution were analyzed using flow cytometry. Levels of Bcl-2 family prot eins 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 ACTS cells were resistant to treatment with IFNs. The IC(50)s of IFN-alpha for TSGH9201 and TMK-1 cells were 300 a nd 500 U/ml, respectively, and the IC(50)s of IFN-gamma were 40 and 2.0 U/m l, respectively. Both IFN-alpha- and IFN-gamma -induced cell cycle arrest i n sensitive cells. IFN-gamma also increased cellular apoptosis, demonstrate d by increasing in situ DNA damage and DNA fragmentation. IFN-gamma increas ed BAK protein levels and decreased Bcl-2 and Bcl-X-S protein levels in TSG H9201 cells. Conclusions: IFN-alpha suppressed growth of gastric cancer cells through in duction of cell cycle arrest. IFN-gamma suppressed cell growth through indu ction of both cell cycle arrest and apoptosis. IFN-gamma -mediated apoptosi s was associated with the alteration in protein levels of Bcl-2, Bcl-X-S an d BAK. J. Surg. Oncol. 2000:75:122-130. (C) 2000 Wiley-Liss, Inc.