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

doi:10.6040/j.issn.1671-7554.0.2014.170

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

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. 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 Yongqiang^1,2, XIE Xiaoye², CHEN Xuemei¹, FENG Huiwei¹, JIA Tao¹, ZHANG Hui¹, FAN Xianliang¹

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

摘要/Abstract

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

赵永强, 谢晓烨, 陈雪梅, 冯慧伟, 贾涛, 张辉, 范献良. 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[J]. 山东大学学报（医学版）, 2014, 52(9): 39-43.

ZHAO Yongqiang, XIE Xiaoye, CHEN Xuemei, FENG Huiwei, JIA Tao, ZHANG Hui, FAN Xianliang. COX-2 specific inhibitor induced apoptosis and autophagy in Hep-2 cells in vitro[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(9): 39-43.

参考文献

[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.

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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

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

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