您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

山东大学学报（医学版） ›› 2014, Vol. 52 ›› Issue (9): 39-43.doi: 10.6040/j.issn.1671-7554.0.2014.170

• 基础医学 • 上一篇    下一篇

COX-2选择性抑制剂诱导人喉癌Hep-2细胞凋亡及自噬的体外研究

赵永强1,2, 谢晓烨2, 陈雪梅1, 冯慧伟1, 贾涛1, 张辉1, 范献良1   

  1. 1. 山东大学第二医院耳鼻咽喉-头颈外科, 山东 济南 250033;
    2. 山东大学医学院, 山东 济南 250012
  • 收稿日期:2014-03-26 修回日期:2014-07-01 出版日期:2014-09-10 发布日期:2014-09-10
  • 基金资助:
    山东省自然科学基金联合专项(ZR2013HL028)

COX-2 specific inhibitor induced apoptosis and autophagy in Hep-2 cells in vitro

ZHAO Yongqiang1,2, XIE Xiaoye2, CHEN Xuemei1, FENG Huiwei1, JIA Tao1, ZHANG Hui1, FAN Xianliang1   

  1. 1. Department of Otorhinolaryngology, the Second Hospital of Shandong University, Jinan 250033, Shandong, China;
    2. School of Medicine, Shandong University, Jinan 250012, Shandong, China
  • Received:2014-03-26 Revised:2014-07-01 Online:2014-09-10 Published:2014-09-10
  • Contact: 范献良。E-mail:sdentfan@126.com E-mail:sdentfan@126.com

PDF (PC)

179

摘要： 目的 初步探讨环氧化酶-2（COX-2）选择性抑制剂塞来昔布对人喉癌Hep-2细胞诱导凋亡的作用及可能的机制并观察其引起的自噬现象。方法 用四甲基偶氮唑盐（MTT）法，检测塞来昔布以不同浓度（0～100μmol/L）及作用时间（0～72h）处理Hep-2细胞后细胞增殖活力的变化；流式细胞仪检测不同浓度及时间塞来昔布处理后Hep-2细胞的凋亡率；透射电镜观察塞来昔布处理后的细胞超微结构改变；Western blotting检测凋亡诱导因子（AIF）移位改变。结果 塞来昔布呈时间和浓度依赖性地抑制Hep-2细胞的增殖；诱导喉癌细胞凋亡并呈浓度依赖性；药物处理72h与48h相比凋亡率的改变无统计学意义（P>0.05），药物处理72 h后在电镜下观察到自噬现象；AIF蛋白逐渐从线粒体释放、移位到细胞核。结论 塞来昔布可诱导喉癌细胞凋亡，其机制涉及非caspase依赖的AIF机制，Hep-2细胞产生的自噬可能会对抗塞来昔布诱导的凋亡。

关键词: Hep-2细胞, 自噬, 塞来昔布, 环氧化酶-2, 凋亡

Abstract: Objective To investigate the ability of celecoxib inducing apoptosis in Hep-2 cells and its possible mechanisms, as well as to observe the autophagy of the cells. Methods MTT was used to observe the proliferation of Hep-2 cells treated with celecoxib at different doses(0-100 μmol/L) and for different hours(0-72 hours). Cell ultrastructure was observed by electron microscope. Hep-2 cells were treated with celecoxib at different doses and for different hours and then the cell apoptosis rate was measured by flow cytometry. AIF expression was examined by Western blotting. Results Celecoxib induced a time- and dose-dependent growth inhibition in Hep-2 cells. It also induced the apoptosis of Hep-2 cells in a dose-dependent manner. No significant difference existed in the apoptosis rate of the cells treated by celecoxib for 72 and 48 hours(P>0.05). Autophagy was observed in Hep-2 cells treated by celscoxib for 72 hours. Celecoxib showed the ability of transporting AIF from mitochondria to cell nucleus. Conclusion Celecoxib can induce cell apoptosis, in which AIF mechanism may be involved. Autophagy induced by celecoxib may protect Hep-2 cells against apoptosis.

Key words: Hep-2 cells, Apoptosis, Celecoxib, Autophagy, Cyclooxygenase-2

中图分类号: 

  • R739.65
[1] Berg J, Christoph T, Bodenteich A, et al. Heterogeneous distribution of COX-2 over-expression in human colon carcinoma cells[J]. Adv Exp Med Biol, 1997, 433(2):327-330.
[2] Perez-Ruiz E, Cazorla O, Redondo M, et al. Immunohistochemical expression of cyclooxygenase-2 in patients with advanced cancer of the larynx who have undergone induction chemotherapy with the intention of preserving phonation[J]. Clin Transl Oncol, 2012, 14(9):682-688.
[3] 孙希才, 葛荣明, 董庆汉, 等. 环氧化酶-2在喉鳞状细胞癌中的表达及其与微血管密度的关系[J]. 临床耳鼻咽喉科学杂志, 2005, 19(21):967-970. SUN Xicai, GE Yongming, DONG Qinghan, et al. The expressiong of cyclooxygenase-2 in laryngeal squamous cell carcinoma and its relationship with MVD[J]. J Clin Otorhinolarvnaol (China), 2005, 19(21):967-970.
[4] Aline C A, Fernanda S G, Felipe F S, et al. Effects of celecoxib treatment over the AKT pathway in head and neck squamous cell carcinoma[J]. J Oral Pathol Med, 2013, 42(10):793-798.
[5] Cho E I, Kowalske D P, Sasaki C T, et al. Tissue microarray analysis reveals prognostic significance of COX-2 expression for local relapse in T1-2N0 larynx cancer treated with primary radiation therapy[J]. Laryngoscope, 2004, 114(11):2001-2008.
[6] Wang Y J, Niu X P, Yang L, et al. Effects of celecoxib on cycle kinetics of gastric cancer cells and protein expression of cytochrome C and Caspase-9[J]. Asian Pac J Cancer Prev, 2013, 14(4):2343-2347.
[7] Bocca C, Bozzo F, Cannito S, et al. Celecoxib inactivates epithelial-mesenchymal transition stimulated by hypoxia and/or epidermal growth factor in colon cancer cells[J]. Mol Carcinog, 2012, 51(10):783-785.
[8] Ramer R, Walther U, Borchert P, et al. Induction but not inhibition of COX-2 confers human lung cancer cell apoptosis by celecoxib[J]. J Lipid Res, 2013, 54(11):3116-3129.
[9] Jeon Y W, Suh Y J. Synergistic apoptotic effect of celecoxib and luteolin on breast cancer cells[J]. Oncol Rep, 2013, 29(2):819-825.
[10] Huang H, Pierstorff E, Osawa E, et al. Active nanodiamond hydrogels for chemotherapeutic delivery[J]. Nano Letters, 2007, 7(11):3305-3314.
[11] Joza N, Susin S A, Daugas E, et al. Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death[J]. Nature, 2001, 410(6828):549-554.
[12] Winkel R R, Kalhauge A, Fredfeldt K E. The useful-ness of ultrasound colour-doppler twinkling artefact for detecting urolithiasis compared with low dose nonenhanced computerized tomography[J]. Ultrasound Med Biol, 2012, 38(7):1180-1187.
[13] Zhou R, Zhang L, Wang R, et al. Effect of celecoxib on proliferation, apoptosis, and survivin expression in human glioma cell line U251[J]. Chin J C, 2010, 29(3):294-299.
[14] Mizushima N, Levine B, Cuervo A M, et al. Autophagy fights disexse through cellular self-digestion[J]. Na-ture, 2008, 451(7182):1069-1075.
[15] Zou Z, Yuan Z, Zhang Q, et al. Aurora kinase A inhibition-induced autophagy triggers drug resistance in breast cancer cells[J]. Autophagy, 2012, 8(12):1798-1810.
[1] 张士宝 刘庆勇 阮喜云 陈杰 张建军 李宗武 杨广笑 王全颖. NT4-SAC-HA2-TAT融合基因表达载体的构建及鉴定[J]. 山东大学学报(医学版), 2209, 47(6): 15-19.
[2] 鹿向东 杨伟 徐广明 曲元明. 脑膜瘤中PPAR-γ的表达及曲格列酮对脑膜瘤培养细胞生长的影响[J]. 山东大学学报(医学版), 2209, 47(6): 65-.
[3] 索东阳,申飞,郭皓,刘力畅,杨惠敏,杨向东. Tim-3在药物性急性肾损伤动物模型中的表达及作用机制[J]. 山东大学学报 (医学版), 2020, 1(7): 1-6.
[4] 赵姗姗,李晓梅,梁婷,张超,宋静,侯桂华. 自噬对125I-anti-TLR5同种移植排斥靶向显像的影响[J]. 山东大学学报（医学版）, 2017, 55(9): 46-52.
[5] 殷雷,殷睿,李文佳,刘帅,吕家驹. CYLD抑制自噬提高膀胱癌细胞吉西他滨化疗敏感性[J]. 山东大学学报（医学版）, 2017, 55(8): 1-6.
[6] 张亮,徐敏,庄向华,娄福臣,娄能俊,吕丽,郭文娟,郑凤杰,陈诗鸿. 内质网应激与凋亡在糖尿病周围神经病变中的表达变化[J]. 山东大学学报（医学版）, 2017, 55(8): 13-17.
[7] 李睿,马伟红,任满意,赵萌萌,姜珊,巨媛媛,郭颖,孙昭辉,隋树建. TWEAK与原发性高血压患者心脏重塑的相关性[J]. 山东大学学报（医学版）, 2017, 55(5): 49-55.
[8] 郭贺贺,孙志强,刘艳娟,刘奕晨,李广,郑方. 去甲斑蝥素对骨髓瘤U266细胞Notch信号通路表达的影响[J]. 山东大学学报（医学版）, 2017, 55(3): 32-37.
[9] 涂云华,陈利远,王喜,周英,康颖倩,薛月萃,荣冬芸,叶振源,曹煜. 芳姜黄酮衍生物对WM35细胞增殖及凋亡的影响[J]. 山东大学学报（医学版）, 2017, 55(2): 68-73.
[10] 巩璐伟,周丽珍,苏国海. 培哚普利通过调节Akt-FoxO1通路保护糖尿病性心肌病大鼠心功能损伤[J]. 山东大学学报（医学版）, 2017, 55(10): 65-70.
[11] 陈琦,李佳琪,郭智彬,贾惊宇,何林生. 环氧化酶-2基因启动子区甲基化水平在子宫内膜异位症中的作用[J]. 山东大学学报（医学版）, 2017, 55(1): 44-48.
[12] 赵路,矫俊,张腾,焦薪霖,崔保霞. 肝X受体在卵巢癌组织中的表达及T0901317在卵巢癌细胞系SKOV3中的作用[J]. 山东大学学报（医学版）, 2017, 55(1): 49-53.
[13] 张琨,张孝国,崔杏杏,陈士俊. 慢性HBV感染者外周血单个核细胞凋亡相关因子的表达及其与乙肝慢性化的关系[J]. 山东大学学报（医学版）, 2016, 54(7): 38-42.
[14] 巨媛媛,任满意,李睿,赵萌萌,隋树建. TWEAK通过ERK1/2通路促进大鼠心肌成纤维细胞MMP2与Ⅰ型胶原表达[J]. 山东大学学报（医学版）, 2016, 54(5): 23-28.
[15] 李红志,刘静,宋岩,迟令懿,刘玉光. 利拉鲁肽对脊髓损伤修复作用的探讨[J]. 山东大学学报（医学版）, 2016, 54(4): 1-5.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发