一氧化氮对鼻咽癌CNE-2细胞株化疗增敏效应的研究

doi:10.6040/j.issn.1673-3770.0.2017.297

摘要/Abstract

摘要： 目的探讨外源性一氧化氮(NO)在顺铂(DDP)作用于CNE-2细胞的过程中是否存在增敏效应,为提高鼻咽癌化疗疗效提供实验和理论依据。方法分别使用不同浓度NO供体药物硝普钠(SNP)、DDP及二者联合干预CNE-2细胞,采用硝酸还原酶法检测NO的浓度,镜下观察细胞形态学变化,CCK-8法检测细胞增殖抑制率以及流式细胞仪检测细胞凋亡。结果 (1) SNP呈浓度依赖方式抑制CNE-2细胞的增殖、促进凋亡;(2) 上清液中NO浓度与SNP浓度呈正相关,有统计学意义(r=0.968, P<0.001);(3) DDP+SNP联合组与SNP组和DDP组相比,CNE-2细胞形态学差异显著, 漂浮细胞显著增多,贴壁数量逐渐减少并失去原有形态;(4) 当SNP 600 μmol/L时对细胞增殖无明显影响,然而联合DDP后较单用DDP组细胞抑制率显著提高(t=9.049, P<0.001);(5) SNP组与DDP联用时CNE-2细胞凋亡率上升,较单用SNP、DDP组显著增强(t=-19.816, P<0.001; t=-5.242, P=0.035)。结论外源性NO能抑制CNE-2的增殖,其抑制效应与NO浓度呈正相关;合适浓度的外源性NO可在对细胞本身不产生明显毒性的情况下显著增强DDP对CNE-2细胞株的化疗敏感性。

关键词: 鼻咽癌, 顺铂, 化疗增敏, 一氧化氮, 硝普钠, 凋亡

Abstract: Objective To investigate whether exogenous nitric oxide(NO)could increase chemosensitization to cisplatin(DDP)in CNE2 cells, and to provide an experimental and theoretical basis for improving the effectiveness of chemotherapy for nasopharyngeal carcinoma. Methods CNE-2 cells were treated with various concentrations of sodium nitroprusside(SNP), DDP, and both chemicals. The nitrate reductase method was used to detect the concentration of NO. Morphological changes of cells were observed using an inverted phase contrast microscope and CCK8 assays were used to examine the viability of cells. Flow cytometry was applied to detect apoptosis in NPC cells. Results (1)The concentration of NO was positively correlated with the concentration of SNP, and this correlation was statistically significant(r=0.968, P<0.05).(2)Compared with the CNE-2 cells in the SNP group, DDP group, and control group, the CNE-2 cells in the DDP+SNP group showed more extensive morphological changes.(3)The inhibitory effects of SNP+DDP were significantly greater than those of SNP or DDP alone(P<0.05).(4)Compared with the groups treated with SNP or DDP individually, flow cytometry showed that the apoptosis rate of CNE-2 cells was significantly higher in the group treated with both SNP and DDP(P<0.05). Conclusion Exogenous NO can inhibit CNE-2 proliferation, and the inhibitory effect was positively correlated with the concentration of NO. The proper concentration of exogenous NO can significantly enhance the chemosensitivity of CNE-2 cells to DDP, without substantial toxicity.

Key words: Nasopharyngeal carcinoma, Sodium nitroprusside, Cis-platinum, Apoptosis, Chemosensitization, Nitric oxide

中图分类号:

R739.62

张彩霞,刘阳云,江文,刘庚勋,曹杭,陈琼,张纪帅. 一氧化氮对鼻咽癌CNE-2细胞株化疗增敏效应的研究[J]. 山东大学耳鼻喉眼学报, 2017, 31(5): 72-78.

ZHANG Caixia, LIU Yangyun, JIANG Wen, LIU Gengxun, CAO Hang, CHEN Qiong, ZHANG Jishuai. Investigation of chemosensitization induced by nitric oxide on nasopharyngeal carcinoma CNE-2 cells.[J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2017, 31(5): 72-78.

参考文献

[1] Tan G, Tang X, Tang F. The role of microRNAs in nasopharyngeal carcinoma[J]. Tumour Biol, 2015, 36(1):69-79.
[2] Razak AR, Siu LL, Liu FF, et al. Nasopharyngeal carcinoma: the next challenges[J]. Eur J Cancer, 2010, 46(11):1967-1978.
[3] Lee AW, Lin JC, Ng WT. Current management of nasopharyngeal cancer[J]. Semin Radiat Oncol, 2012, 22(3):233-244.
[4] Perri F, Bosso D, Buonerba C, et al. Locally advanced nasopharyngeal carcinoma: current and emerging treatment strategies[J]. World J Clin Oncol, 2011, 2(12):377-383.
[5] Zhang L, Chen QY, Liu H, et al. Emerging treatment options for nasopharyngeal carcinoma[J]. Drug Des Devel Ther, 2013, 7(2):37-52.
[6] 张彩霞, 刘阳云. 一氧化氮对肿瘤细胞化疗增敏机制研究进展[J]. 临床与病理杂志,2016,36(8):1224-1229. ZHANG Caixia, LIU Yangyun. Research progress of nitric oxide chemosensitization mechanisms on tumor cells[J]. Inter J Pathol Clin Med, 2013, 7(2):37-52.
[7] Yang L, Lan C, Fang Y, et al. Sodium nitroprusside(SNP)sensitizes human gastric cancer cells to TRAIL-induced apoptosis[J]. Int Immunopharmacol, 2013, 17(2):383-389.
[8] Seabra AB, de Lima R, Calderón M. Nitric oxide releasing nanomaterials for cancer treatment: current status and perspectives[J]. Curr Top Med Chem, 2015, 15(4):298-308.
[9] Zhang HX, Deng C, Liu OS, et al. Inducible nitric oxide inhibitor enhances the anti-tumor effect of cisplatin on CNE-2 cells by inducing cell apoptosis[J]. Eur Rev Med Pharmacol Sci, 2014, 18(19):2789-2797.
[10] 刘阳云, 赵素萍, 刘庚勋, 等. 诱导型一氧化氮合酶在指导晚期鼻咽癌治疗方案选择中的价值[J]. 中国癌症杂志,2007,17(9):684-688. LIU Yangyun, ZHAO Suping, LIU Gengxun, et al. The value of inducible nitric oxide synthase to select the project of treatment in nasopharyngeal carcinoma[J]. Chin Oncol, 2007, 17(9):684-688.
[11] 刘阳云, 赵素萍, 刘庚勋, 等. 诱导型一氧化氮合酶与环氧合酶-2在鼻咽癌中表达的初步研究[J]. 中华放射肿瘤学杂志,2007,16(2):155-156.
[12] Mocellin S. Nitric oxide: cancer target or anticancer agent?[J]. Curr Cancer Drug Targets, 2009, 9(2):214-236.
[13] 张彩霞,刘阳云. 一氧化氮供体型化合物化疗增敏效应[J]. 国际肿瘤学杂志,2016,43(9):53-56. ZHANG Caixia, LIU Yangyun. Neoplasms chemosensitization enhancing effects of nitric oxide donor compounds[J]. J Int Oncol, 2016, 43(9):53-56.
[14] Hirst D, Robson T. Nitric oxide in cancer therapeutics: interaction with cytotoxic chemotherapy[J]. Curr Pharm Des, 2010, 16(4):411-420.
[15] Carradori S, Mollica A, Monte CD, et al. Nitric oxide donors and selective carbonic anhydrase inhibitors: a dual pharmacological approach for the treatment of glaucoma, cancer and osteoporosis[J]. Molecules, 2015, 20(4):5667-5679.
[16] Reynolds MM, Witzeling SD, Damodaran VB, et al. Applications for nitric oxide in halting proliferation of tumor cells[J]. Biochem Biophys Res Commun, 2013, 4(31):647-651.
[17] Persson PB, Bondke Persson A. Nitric oxide: a classic revisited[J]. Acta Physiol, 2013, 207(3):427-429.
[18] Aranda E, López-Pedrera C, De La Haba-Rodriguez JR, et al. Nitric oxide and cancer: the emerging role of S-nitrosylation[J]. Curr Mol Med, 2012, 12(1):50-67.
[19] Singh S, Gupta AK. Nitric oxide: role in tumour biology and iNOS/NO-based anticancer therapies[J]. Cancer Chemother Pharmacol, 2011, 67(6):1211-1224.
[20] González R1, Ferrín G, Aguilar-Melero P, et al. Targeting hepatoma using nitric oxide donor strategies[J]. Antioxid Redox Signal, 2013, 18(5):491-506.
[21] Huerta-Yepez S, Baritaki S, Baay-Guzman G, et al. Contribution of either YY1 or Bcl XL-induced inhibition by the NO-donor DETANONOate in the reversal of drug resistance, both in vitro and in vivo. YY1 and BclXL are overexpressed in prostate cancer[J]. Nitric Oxide Soc, 2013, 29(1):17-24.
[22] Bian K, Murad F. sGC-cGMP signaling: target for anticancer therapy[J]. Adv Exp Med Biol, 2014, 14(8):5-13.
[23] Bian K, Murad F. What is next in nitric oxide research? From cardiovascularsystem to cancer biology[J]. Nitric Oxide, 2014, 4(3):3-7.
[24] Bonavida B, Garban H. Nitric oxide-mediated sensitization of resistant tumor cells to apoptosis by chemo-immunotherapeutics[J]. Redox Biol, 2015, 10(6):486-494.
[25] Sarti P, Forte E, Mastronicola D, et al. Cytochrome c oxidaseand nitric oxide in action: molecular mechanisms and pathophysiological implications[J]. Biochim Biophys Acta, 2012, 18(7):610-619.
[26] Bonavida B, Baritaki S. The novel role of yin yang 1 in the regulation of epithelial to mesenchymal transition in cancer via the dysregulated NF-κB/Snail/YY1/RKIP/PTEN circuitry[J]. Crit Rev Oncog, 2011, 16(4):211-226.
[27] Baritaki S, Huerta-Yepez S, Sahakyan A, et al. Mechanisms of nitric oxide-mediated inhibition of EMT in cancer: inhibition of the metastasis-inducer snail and induction of the metastasis-suppressor RKIP[J]. Cell Cycle, 2010, 12(9):4931-4940.
[28] Tang H, Park S, Sun SC, et al. Kolcgnaling components of the IκB kinase complex[J]. FEBS Lett, 2010, 5(8):662-668.
[29] Domingo E, Church DN, Sieber O, et al. Evaluation of PIK3 CA mutation as a predictor of benefit from nonsteroidal anti-inflammatory drug therapy in colorectal cancer[J]. J Clin Oncol, 2013, 31(4):4297-4234.

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