多西紫杉醇对人鼻咽癌CNE-2细胞辐射敏感性及侵袭转移相关因子表达的影响

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (6): 620-625.

多西紫杉醇对人鼻咽癌CNE-2细胞辐射敏感性及侵袭转移相关因子表达的影响

林素芳

温岭市第一人民医院, 静脉用药调配中心, 温岭 317500, 浙江

收稿日期:2013-10-07 修回日期:2014-04-22 发布日期:2014-07-01
作者简介:林素芳, 女, 本科, 主管药师, 研究方向:临床用药配制监测。Tel: 15167652121 E-mail: linsufangedu@126.com

Effects of docetaxel on the radiation sensitivity and expression of invasion and metastasis relative factors of human Nasopharyngeal Cancer CNE-2 cells

LIN Su-fang

People's First Hospital of Wenling, Pharmacy Intravenous Admixture Services, Wenling 317500, Zhejiang, China

Received:2013-10-07 Revised:2014-04-22 Published:2014-07-01

摘要/Abstract

摘要： 目的: 研究多西紫杉醇(docetaxel)对人鼻咽癌CNE-2细胞放疗敏感性的作用及对侵袭转移相关因子MMP-2、MMP-9表达的影响。方法: 采用CCK-8法检测多西紫杉醇对CNE-2细胞增殖能力的影响, 克隆形成实验测定多西紫杉醇对细胞放疗敏感性, 化学发光法检测MMP-2启动子质粒转染细胞后双荧光素酶活性, 荧光定量PCR法检测细胞MMP-2、MMP-9 mRNA表达, Western blot法检测细胞MMP-2、MMP-9蛋白表达。结果: 多西紫杉醇对CNE-2细胞增殖有明显的抑制作用, 24、48、72 h 的IC₅₀值分别为 30.6、25.4、12.8 μmol/L;无毒剂量(5 μmol/L)多西紫杉醇处理CNE-2细胞后, 其对放疗的敏感性明显增强(P<0.05), MMP-2启动子活性比未处理组显著降低;MMP-2和MMP-9基因mRNA和蛋白表达均较未处理组下降。结论: 多西紫杉醇联合放疗能显著提高人鼻咽癌CNE-2细胞的放射敏感性, 其作用机制可能与其抑制细胞内MMP-2、MMP-9基因转录, 下调细胞内MMP-2、MMP-9蛋白表达有关。

关键词: 鼻咽癌, 多西紫杉醇, 辐射耐受性, 侵袭转移

Abstract: AIM : To investigate the role of docetaxel on the radiosensitivity of human nasopharyngeal cancer CNE-2 cell, and the effect on expression of invasion and metastasis relative factors MMP-2 and MMP-9.METHODS: The effects of docetaxel on cell proliferation abilities of CNE-2 cells were detected by CCK-8. The radiosensitivity of cells to docetaxel was examined by clone formation assay. The dual luciferase reporter assay was used to observe the activity of MMP-2 promoter after transduction 48 h later. Expressions of MMP-2 and MMP-9 mRNA in cells were detected by Real-time PCR and protein expressions of MMP-2 and MMP-9 were assayed by Western blot.RESULTS:Docetaxel had obvious inhibition on proliferation of CNE-2 cells, the 50% inhibiting concentration (IC₅₀) was respectively 30.6, 25.4, 12.8 μmol/L in 24, 48, and 72 h, and innocuity dose in 24 h was 5 μmol/L. The radiosensitivity of CNE-2 cells was enhanced obviously and activity of MMP-2 promoter was decreased after administration with docetaxel in 5 μmol/L (P<0.05). Expressions of MMP-2 and MMP-9 mRNA and protein in cells were down-regulated compare to untreated groups.CONCLUSION: Docetaxel administration with radio- therapy can increase the radiation sensitivity of CNE-2 cells. This mechanism may be related to the inhibiting genetic transcription of MMP-2 and MMP-9 in cells, and down-regulation protein expression of MMP-2 and MMP-9.

Key words: nasopharyngeal carcinoma, docetaxel, radiation tolerance, invasion and metastasis

中图分类号:

R965.2

林素芳. 多西紫杉醇对人鼻咽癌CNE-2细胞辐射敏感性及侵袭转移相关因子表达的影响[J]. 中国临床药理学与治疗学, 2014, 19(6): 620-625.

LIN Su-fang. Effects of docetaxel on the radiation sensitivity and expression of invasion and metastasis relative factors of human Nasopharyngeal Cancer CNE-2 cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(6): 620-625.

参考文献

[1] Banjat B, Audry H, Bourhis J, et al. Chemotherapyin locally advanced nasopharyngeai carcinoma anindividual patient data meta-analysis of eight raildomizedtrials and l753 patients[J]. Int Radiat Oncol Biol Phys, 2006, 64(1): 47-56.
[2] 王若峥, 张国庆. 肿瘤放射治疗学[M]. 北京: 科学出版社, 2010: 357-369.
[3] Ali H, Al Sarraf M. Chemotherapy in advanced nasopharyngeal cancer[J]. Oncology (Williston Park), 2000, 14(8): 1223-1230.
[4] Aujat B, Auary H, Bourhis J, et al. Chemotherapy as an adjunct to radiotherapy in locally advanced nasopharyngeal carcinoma[J]. Cochrane Database Syst Rev, 2006, 18(4): CD004329.
[5] Alarraf M, Le Blanc M, Giri PG, et al. Chemoradio therapy versus radiotherapy in patients with advanced nasopharyngeal cancer: Phase Ⅲ randomized Inter group Study 0099[J]. J Clin Oncol, 1998, 16(4): 1310-1317.
[6] 吕志倩. 放疗联合多西紫杉醇治疗局部中晚期鼻咽癌的临床观察[J]. 中国医药指南, 2011, 9(11): 117-118.
[7] 林秀欣, 邓文静, 陈秋莲. 多西紫杉醇联合放疗治疗中晚期鼻咽癌临床观察[J]. 河北医学, 2010, 16(8): 931-933.
[8] Ngeow J, Lim WT, Leong SS, et al. Docetaxel is effective in heavily pretreated patients with disseminated nasopharyngeal carcinoma[J]. Ann Oncol, 2011, 22(3): 718-722.
[9] 潘素明, 陈志仁, 彭少华, 等. 少量多西紫杉醇对局部晚期鼻咽癌放射增敏的疗效观察[J]. 临床医药实践杂志, 2007, 10(S2): 678-680.
[10]Wolafiska M, Sobolewski K, Bafikowski E, et al. Matrix metaliopmteinases of human leiomyoma in various stages of tumor growth[J]. Gyrnecol Obstet Invest, 2004, 58(1): 14-18.
[11]Visse R, Nagaso H. Matrix metalloproteinases and tissue iIlllibitom of metallopmteinases: structure, function, and biochemistry[J]. Circ Res, 2003, 92(8): 827-839.

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