Shyu R Y, Su H L, Yu J C, Jiang S Y
Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
J Surg Oncol. 2000 Oct;75(2):122-30. doi: 10.1002/1096-9098(200010)75:2<122::aid-jso9>3.0.co;2-4.
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.
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.
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.
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.
干扰素（IFN）通过免疫调节或直接抗肿瘤作用发挥抗肿瘤活性。我们研究了α干扰素和γ干扰素对TSGH9201、TMK-1和AGS胃癌细胞体外生长的活性及机制。
通过测量细胞总DNA分析干扰素对细胞生长的活性。通过原位DNA断裂和DNA梯带的形成评估干扰素对细胞凋亡的影响。使用流式细胞术分析干扰素对细胞周期阶段分布的影响。使用蛋白质印迹法分析干扰素处理后Bcl-2家族蛋白的水平。
α干扰素和γ干扰素均能有效抑制TSGH9201和TMK-1细胞的生长，而AGS细胞对干扰素处理具有抗性。α干扰素对TSGH9201和TMK-1细胞的半数抑制浓度（IC50）分别为300和500 U/ml，γ干扰素的IC50分别为40和2.0 U/ml。α干扰素和γ干扰素均可诱导敏感细胞的细胞周期停滞。γ干扰素还可增加细胞凋亡，表现为原位DNA损伤和DNA片段化增加。γ干扰素可增加TSGH9201细胞中BAK蛋白水平，降低Bcl-2和Bcl-X(S)蛋白水平。
α干扰素通过诱导细胞周期停滞抑制胃癌细胞生长。γ干扰素通过诱导细胞周期停滞和凋亡抑制细胞生长。γ干扰素介导的凋亡与Bcl-2、Bcl-X(S)和BAK蛋白水平的改变有关。
