干扰素α对Raji 细胞的生长抑制作用及其作用机制

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (3): 270-274.

干扰素α对Raji 细胞的生长抑制作用及其作用机制

刘加军, 伍新尧, 蔡贵庆, 伍祥林, 童大跃, 陈丽娴, 潘祥林¹, 陈春燕¹

中山大学中山医学院法医生物医学实验室, 广州510080, 广东;
¹山东大学第二医院血液肿瘤中心, 济南250033, 山东

收稿日期:2003-11-11 接受日期:2003-12-05 出版日期:2004-03-26 发布日期:2020-11-21

Anti-proliferation effect of interferon-αon Raji cells and its mechanism

LIU Jia-Jun, WU Xin-Yao, CAI GUI-Qing, WU Xiang-Lin, TONG Da-Yue, CHEN Li-Xian, PAN Xiang-Lin¹, CHEN Chun-Yan¹

Lab of Forensic and Biological Science, Medical College of Sun Yat-Sen University, Guangzhou 510080, Guangdong, China;
¹Central Department of Heamatology and Oncology, the second Hospital of Shandong University, Jinan 250033, Shandong, China

Received:2003-11-11 Accepted:2003-12-05 Online:2004-03-26 Published:2020-11-21
Contact: WU Xin-Yao, male, tutor, professor, specialized in tumor gene therapy.Tel:020-87330557 　Fax:020-87330302 　E-mail:xyaow@zsums.edu.cn
About author:LIU Jia-Jun, male, Ph.D, post-doctoral fellow, majoring in heamatology and oncology.Tel:020-88369856 　E-mail:liujj@gzsums.edu.cn

摘要/Abstract

摘要： 目的:探讨干扰素α对白血病Raji 细胞生长的抑制作用及其作用机制。方法:以不同浓度的干扰素α作用于体外培养的Raji 细胞, 应用MTT 法检测细胞生长抑制率, 流式细胞仪检测细胞凋亡率,Hoechst 33258 荧光染色法观察细胞凋亡, TRAP-PCRELISA法检测细胞凋亡前后的端粒酶活性。结果:5×10³ U·ml-1以上的干扰素α可显著降低Raji 细胞端粒酶活性, 抑制细胞的生长及诱导细胞发生凋亡,并呈现出明显的量-效与时-效关系。药物(10 ×10³ U·ml^-1) 作用48 ～ 60 h 在Hoechst 染色图片上可见核浓缩及核碎裂等典型的凋亡改变。结论:干扰素α能抑制Raji 细胞的生长并诱导细胞发生调亡,降低细胞端粒酶活性可能是其重要作用机制之一;这为干扰素应用于临床治疗淋巴瘤细胞白血病提供了有力的试验依据。

关键词: 干扰素α, 白血病, 端粒酶, 细胞凋亡, Raji细胞

Abstract: AIM: To investigate the anti-proliferation effect of interferon-α(IFN-α) on leukemic Raji cells and its mechanism.METHODS: Raji cells were given different concentrations of INF-α.The inhibitory rate of the cells was measured by MTT assay, apoptotic rate was detected by flow cytometry (FCM), morphology of cell apoptosis was observed by Hoechst 33258 fluorescence staining, and the activity of telomerase was detected by PCRELISA before and after apoptosis occurred.RESULTS: IFN-α(over 5 ×10³ U·ml^-1) could cause apoptosis significantly, decrease the telomerase activity, and inhibit the growth of Raji cells in time-and dose-dependent manner.Marked morphological changes of cell apoptosis including chromosome condensation and nuclear fragmentation were observed very clearly by Hoechst 33258 fluorescence staining especially after the cells treated with IFN-α for 48-60 h.CONCLUSION: IFN-αhas apparent antiproliferation and apoptotic effects on Raji cells in vitro, and one of the most important mechanisms may be decrease of the telomerase activity of Raji cells.These results will provide strong laboratory evidence of IFN-αin the clinical treatment of lymphoma cell leukemia.

Key words: interferon-α, leukemia, telomerase, apoptosis, Raji cells

中图分类号:

刘加军, 伍新尧, 蔡贵庆, 伍祥林, 童大跃, 陈丽娴, 潘祥林, 陈春燕. 干扰素α对Raji 细胞的生长抑制作用及其作用机制[J]. 中国临床药理学与治疗学, 2004, 9(3): 270-274.

LIU Jia-Jun, WU Xin-Yao, CAI GUI-Qing, WU Xiang-Lin, TONG Da-Yue, CHEN Li-Xian, PAN Xiang-Lin¹, CHEN Chun-Yan¹. Anti-proliferation effect of interferon-αon Raji cells and its mechanism[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(3): 270-274.

参考文献

1 Leclerc S, Myers RP, Moussalli J, Herson S, Poynard T, Benveniste O.Sarcoidosis and interferon therapy:report of five cases and review of the literature[J].Eur J Intern Med, 2003;14 (4):237-43
2 Keating A.Chronic myeloid leukemia:current therapies and the potential role of farnesyl transferase inhibitors[J].Semin Hematol, 2002;39(3):11-7
3 Blankenstein T, Qin Z.The role of IFN-gamma in tumor transplantation immunity and inhibition of chemical carcinogenesis [J].Curr Opin Immunol, 2003;15(2):148-54
4 Chawla-Sarkar M, Lindner DJ, Liu YF, Williams BR, Sen GC, Silverman RH, et al.Apoptosis and interferons:role of interferon-stimulated genes as mediators of apoptosis[J].Apoptosis, 2003;8(3):237-49
5 Chada S, Ramesh R, Mhashilkar AM.Cytokine-and chemokine-based gene therapy for cancer[J].Curr Opin Mol Ther, 2003;5(5):463-74
6 Lehtonen A, Lund R, Lahesmaa R, Julkunen I, Sareneva T, Matikainen S.IFN-alpha and IL-12 activate IFN regulatory factor 1 (IRF-1), IRF-4, and IRF-8 gene expression in human NK and T cells[J].Cytokine, 2003 Nov 7;24(3):81-90
7 Minami R, Muta K, Ilseung C, Abe Y, Nishimura J, Nawata H.Interleukin-6 sensitizes multiple myeloma cell lines for apoptosis induced by interferon-a[J].Exp Hematol, 2000;28(3): 244-7
8 Keating A.Chronic myeloid leukemia:current therapies and the potential role of farnesyl transferase inhibitors[J].Semin Hematol, 2002;39:11-7
9 Mokbel K.The evolving role of telomerase inhibitors in the treatment of cancer[J].Curr Med Res Opin, 2003;19(6):470-2
10 Ohyashiki JH, Sashida G, Tauchi T, Ohyashiki K.Telomeres and telomerase in hematologic neoplasia[J].Oncogene, 2002; 21(4):680-7
11 Nakajima A, Tauchi T, Sashida G, Sumi M, Abe K, Yamamoto K, et al.Telomerase inhibition enhances apoptosis in human acute leukemia cells:possibility of antitelomerase therapy[J].Leukemia, 2003;17(3):560-7

[1]	肖悦, 李唐菲, 薛乾富. 聚乙二醇干扰素-α治疗原发性血小板增多症的疗效和安全性分析[J]. 中国临床药理学与治疗学, 2023, 28(9): 1049-1055.
[2]	杨晓佳, 江萌, 吴敏, 张伊黎, 吕兰, 吴嫄芬, 王鑫昱, 刘立权. 藏红花素介导DKK3调控GSK-3β/β-catenin通路对阿尔兹海默症大鼠的认知改善作用[J]. 中国临床药理学与治疗学, 2023, 28(5): 489-497.
[3]	王剑, 孙永东, 周兴玮, 刘雷, 陈龙, 童兴科, 朱佳丽. 黄芩素经由miR-125b-5p/IRF4轴进而促进喉癌细胞死亡并抑制其侵袭的机制研究[J]. 中国临床药理学与治疗学, 2023, 28(11): 1209-1218.
[4]	华海燕, 严杰, 秦宇芬. 五味子乙素通过抑制心肌细胞凋亡减轻大鼠心肌缺血再灌注损伤的实验研究[J]. 中国临床药理学与治疗学, 2022, 27(8): 848-856.
[5]	李雪恒, 李龙. 褪黑素与特发性肺纤维化关系的研究进展[J]. 中国临床药理学与治疗学, 2022, 27(6): 715-720.
[6]	李莹, 姚伟, 王萌, 余志宏, 龚园其, 蓝海兵, 齐协飞. 鸢尾素通过NF-κB和JNK信号通路减轻屋尘螨诱导的气道上皮细胞炎症及凋亡的实验研究[J]. 中国临床药理学与治疗学, 2022, 27(10): 1106-1112.
[7]	刘云帆, 杜月梅, 刘晓艺, 高丽萍. 枸杞多糖对顺铂诱导小鼠睾丸支持细胞凋亡的影响[J]. 中国临床药理学与治疗学, 2021, 26(6): 624-630.
[8]	张伟萍, 江建军, 陈晓锋, 许莎莎. 栀子苷通过抑制VPO1/ERK1/2信号通路减轻糖尿病心肌病大鼠的心肌细胞凋亡[J]. 中国临床药理学与治疗学, 2021, 26(2): 129-136.
[9]	沈芸, 张占丰, 王红灵, 赵冀安. 丹酚酸对大鼠骨骼肌缺血再灌注损伤的保护[J]. 中国临床药理学与治疗学, 2020, 25(10): 1111-1118.
[10]	滕晓晶，董学妍，王智毅，余道军，王贤军. 扶正康复合剂联合顺铂抑制胃癌SGC7901细胞荷瘤裸鼠肿瘤增殖作用的实验研究[J]. 中国临床药理学与治疗学, 2019, 24(7): 744-749.
[11]	张丹阳，董晓敏，周晓焕，张越，张娟，周合冰. 基于GEO数据库筛查急性淋巴细胞白血病糖皮质激素耐药相关基因[J]. 中国临床药理学与治疗学, 2019, 24(3): 272-277.
[12]	孔令宇，席錾，杨亚勤，马文婷，吴畏，郝同琴. 地塞米松对小鼠急性胰腺炎胰腺组织中Notch信号及凋亡相关基因表达的影响[J]. 中国临床药理学与治疗学, 2019, 24(2): 134-139.
[13]	鲍静，李小枫，章涵硕，许庆庆，孟晓明，黄成，李俊. RAB32对慢性粒细胞白血病K562细胞增殖和迁移作用的研究[J]. 中国临床药理学与治疗学, 2019, 24(12): 1321-1327.
[14]	齐冰丽，黄平，颜瑞雪，李倩. 柚皮素通过PI3K/AKT/NF-κB通路抑制卵巢癌细胞增殖和侵袭、诱导凋亡作用的研究[J]. 中国临床药理学与治疗学, 2019, 24(11): 1234-1241.
[15]	曹迎亚，陈群，王箴，吴敬医，姜小敢，金孝岠，鲁卫华. 巨噬细胞在脂多糖诱导肠上皮细胞凋亡中的作用[J]. 中国临床药理学与治疗学, 2019, 24(10): 1142-1146.