PDCD4增强鼻咽癌细胞系CNE1对顺铂化疗敏感性机制研究

doi:10.12092/j.issn.1009-2501.2019.01.002

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (1): 9-13.doi: 10.12092/j.issn.1009-2501.2019.01.002

PDCD4增强鼻咽癌细胞系CNE1对顺铂化疗敏感性机制研究

李琳¹，王文红²，王洪梅³

¹山东省菏泽医学专科学校药理学教研室，菏泽 274000，山东； ²菏泽市立医院耳鼻喉科，菏泽 274000，山东； ³山东大学附属淄博市中心医院，淄博 255036，山东

收稿日期:2018-09-10 修回日期:2018-10-20 出版日期:2019-01-26 发布日期:2019-01-25
通讯作者: 王文红，男，硕士，主治医师，研究方向：鼻咽癌基础与临床。 Tel：15898660091 E-mail：honeyaa@sohu.com
作者简介:李琳，女，硕士，讲师，研究方向：肿瘤临床药物治疗。 Tel：15898660090 E-mail：52746977@qq.com
基金资助:
国家自然科学基金青年科学基金项目（81602327）

PDCD4 enhances the sensitivity mechanism of nasopharyngeal carcinoma cell line CNE1 to cisplatin chemotherapy

LI Lin¹, WANG Wenhong², WANG Hongmei³

¹Department of Pharmacology, Heze Medical College, Heze 274000, Shandong, China; ²Otorhinolaryngological Department, Municipal Hospital of Heze, Heze 274000, Shandong,China; ³ Central Hospital of Zibo Affiliated to Shandong University, Zibo 255036, Shandong, China

Received:2018-09-10 Revised:2018-10-20 Online:2019-01-26 Published:2019-01-25

摘要/Abstract

摘要：

目的: 探讨抑癌基因程序性细胞死亡因子4（the programmed cell death 4,PDCD4）在促进化疗药物顺铂（CDDP）诱导肿瘤细胞凋亡中的作用及可能的机制。方法: CCK8法检测人鼻咽癌系CNE1细胞转染PDCD4前后对CDDP导致的细胞毒性作用影响；Annexin V/FITC和PI凋亡检测转染PDCD4前后对CDDP诱导凋亡的作用；Western blot实验初步探讨其可能的分子机制。结果: PDCD4增强CDDP对人鼻咽癌系CNE1细胞的杀伤作用；PDCD4增加CDDP诱导人鼻咽癌系CNE1细胞凋亡率；机制研究发现PDCD4显著降低人鼻咽癌系CNE1细胞中Twist及MDR1蛋白的表达量，从而促进化疗敏感性。结论: PDCD4通过抑制Twist蛋白增强化疗药物敏感性，提示其参与了鼻咽癌化疗治疗进程。

关键词: 鼻咽癌, PDCD4, Twist, 顺铂

Abstract:

AIM: To investigate the roles of PDCD4 involved in promoting cisplatin (CDDP) induced tumor cell apoptosis. METHODS: CCK8 method was used to detect the cytotoxicity induced by CDDP in human nasopharyngeal carcinoma cell line(CNE1) before and after PDCD4 transfection. The rate of apoptosis for CDDP-induced nasopharyngeal carcinoma cells was investigated using flow cytometry before and after transfection of PDCD4. Western blot method was used to probe the molecular mechanisms involved in the chemosensitivity. RESULTS: PDCD4 enhanced the killing effect of CDDP on human nasopharyngeal carcinoma cell line CNE1; PDCD4 increased CDDP-induced apoptotic rate of human nasopharyngeal carcinoma cell line CNE1; mechanism study found that PDCD4 significantly decreased the expression of Twist and MDR1 protein, thereby promoting the cell chemosensitivity. CONCLUSION: PDCD4 enhances the sensitivity of chemotherapy drugs by inhibiting Twist protein, suggesting that PDCD4 might serve as a chemotherapy target in nasopharyngeal carcinoma treatment.

Key words: nasopharyngeal carcinoma, PDCD4, Twist, cisplatin

中图分类号:

739.6
R965.2

李琳，王文红，王洪梅. PDCD4增强鼻咽癌细胞系CNE1对顺铂化疗敏感性机制研究[J]. 中国临床药理学与治疗学, 2019, 24(1): 9-13.

LI Lin, WANG Wenhong, WANG Hongmei. PDCD4 enhances the sensitivity mechanism of nasopharyngeal carcinoma cell line CNE1 to cisplatin chemotherapy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(1): 9-13.

参考文献

［1］Wang Q, Yang HS. The role of Pdcd4 in tumour suppression and protein translation［J］. Biol Cell,2018，doi:10.1111/boc.201800014.［Epub ahead of print］.
［2］Asangani IA,Rasheed SA,Nikolova DA,et al.MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion,intravasation and metastasis in colorectal cancer［J］.Oncogene,2008,27(15):2128-2136.
［3］Wei X, Wang W, Wang L, et al. MicroRNA-21 induces 5-fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4［J］. Cancer Med,2016,5(4):693-702.
［4］Ning S, Yao M, Wu Y, et al. Correlation of variable repeat number in the neck regions of DC-SIGN and DC-SIGNR with susceptibility to nasopharyngeal carcinoma in a Chinese population［J］. Cancer Manag Res, 2018,10:3193-3198.
［5］马俊,张大为,伍丽娟,等. 鼻咽癌患者血清抗EB病毒潜伏膜蛋白2A抗体的检测及其临床意义［J］. 中国临床药理学与治疗学, 2016,21(8): 890-893.
［6］Huang C, Huang S, Li H, et al. The effects of ultrasound exposure on P-glycoprotein-mediated multidrug resistance in vitro and in vivo［J］. J Exp Clin Cancer Res, 2018,37(1):232.
［7］李晖,陈俊,徐彩虹,等. 丹酚酸A抗肿瘤作用及对逆转A549/MTX肿瘤多药耐药的影响［J］. 中国临床药理学与治疗学, 2017,22(11): 1244-1247.
［8］Stupp R, Hegi ME, van den Bent MJ, et al. Changing paradigms-an update on the multidisciplinary management of malignant glioma［J］. Oncologist, 2006,11(2):165-180.
［9］Bahr O, Rieger J, Duffner F, et al. P-glycoprotein and multidrug resistance-associated protein mediate specific patterns of multidrug resistance in malignant glioma cell lines, but not in primary glioma cells［J］. Brain Pathol, 2003,13(4):482-494.
［10］Vikhreva PN, Shepelev MV, Korobko EV, et al. Pdcd4 tumor suppressor: properties, functions, and their application to oncology［J］. Mol Gen Mikrobiol Virusol, 2010, (2):3-11.
［11］Long J, Yin Y, Guo H, et al. The mechanisms and clinical significance of PDCD4 in colorectal cancer［J］. Gene,2018,34(680):59-64.
［12］Shiota M, Izumi H, Tanimoto A, et al. Programmed cell death protein 4 down-regulates Y-box binding protein-1 expression via a direct interaction with Twist1 to suppress cancer cell growth［J］. Cancer Res,2009,69(7):3148-3156.
［13］Li R, Wu C, Liang H, et al. Knockdown of TWIST enhances the cytotoxicity of chemotherapeutic drugs in doxorubicin-resistant HepG2 cells by suppressing MDR1 and EMT［J］. Int J Oncol, 2018, 53(4):1763-1773.

[1]	周欢, 徐铭, 李波, 刘春英, 王淳. PI3K/Akt/FOXO3a信号通路介导的保护性自噬参与肺腺癌获得性顺铂耐药表型重塑[J]. 中国临床药理学与治疗学, 2022, 27(9): 961-970.
[2]	王新丽, 许霞青, 方寒冰, 郭玉忠. 佛波酯增强顺铂的抗肿瘤活性及降低其肾毒性的作用研究[J]. 中国临床药理学与治疗学, 2022, 27(5): 535-543.
[3]	崔华, 燕红霞, 尹梅. 下调lncRNA LINC00176对肺癌A549/DDP细胞顺铂耐药和自噬的影响[J]. 中国临床药理学与治疗学, 2021, 26(6): 616-623.
[4]	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.
[5]	沈龙德, 李爱禄, 李丽春, 吴银银, 沈龙源, 江秋霞, 贺锦曦, 吴志芬, 余黎吉, 张晓红. 姜黄素对大鼠子宫内膜异位症影响的实验研究#br#[J]. 中国临床药理学与治疗学, 2020, 25(8): 862-868.
[6]	侯彬, 黄维平, 尹中普, 胡守森. lncRNA PCAT19吸附miR-142-5p调控ING3基因表达抑制鼻咽癌细胞的增殖和侵袭[J]. 中国临床药理学与治疗学, 2020, 25(7): 721-727.
[7]	程建平, 李珍, 赵晓琳, 杨梦媛, 冀希炜, 于久飞. 结肠癌患者血清中miR-186-5p表达的研究[J]. 中国临床药理学与治疗学, 2020, 25(10): 1097-1104.
[8]	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.
[9]	赵丽，华夏，谭晔，胡承莲. 萝卜硫素介导Akt/p70S6K信号传导诱导人鼻咽癌CNE-2细胞凋亡[J]. 中国临床药理学与治疗学, 2019, 24(7): 786-791.
[10]	郑中秋，谢伯剑，崔斌斌，柯抒晨，林义. miR-106 b在乳腺癌组织中的表达及其增强乳腺癌细胞顺铂化疗敏感性的机制研究[J]. 中国临床药理学与治疗学, 2019, 24(5): 541-545.
[11]	秦博宇，王刚，齐晓光，王雅捷，孙琼，孙胜杰 . 顺铂与唑来膦酸序贯应用抑制肺癌细胞增殖的研究[J]. 中国临床药理学与治疗学, 2018, 23(9): 1027-1030.
[12]	王秀，刘健，张竞竞，朱娜，王清清，李见春. 17-DMAG对鼻咽癌细胞株HNE1增殖与凋亡的影响[J]. 中国临床药理学与治疗学, 2017, 22(5): 490-494.
[13]	刘文成，谭布珍，占欣璐，胡辉，黄根华，曹青. 雷公藤多苷增强耐顺铂人上皮性卵巢癌SKOV3/DDP细胞株顺铂敏感性的体外研究[J]. 中国临床药理学与治疗学, 2017, 22(12): 1364-1370.
[14]	马俊，张大为，伍丽娟，严仁纯，吴礼锋，刘少峰. 鼻咽癌患者血清抗EB病毒潜伏膜蛋白2A抗体的检测及其临床意义[J]. 中国临床药理学与治疗学, 2016, 21(8): 890-893.
[15]	蔡传书，王培荣，黄雄. 鼻咽癌患者氟尿嘧啶药时曲线下面积与近期疗效及不良反应的相关性分析[J]. 中国临床药理学与治疗学, 2016, 21(12): 1394-1398.

PDCD4增强鼻咽癌细胞系CNE1对顺铂化疗敏感性机制研究

PDCD4 enhances the sensitivity mechanism of nasopharyngeal carcinoma cell line CNE1 to cisplatin chemotherapy

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价