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

doi:10.12092/j.issn.1009-2501.2019.01.002

Abstract

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

CLC Number:

739.6
R965.2

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.

References

［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]	WANG Xinli, XU Xiaqing, FANG Hanbing, GUO Yuzhong. Study of TPA on enhancing the anti-tumor effects of cisplatin and reducing its renal toxicity [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(5): 535-543.
[2]	CUI Hua, YAN Hongxia, YIN Mei. Effects of down-regulating lncRNA LINC00176 on cisplatin resistance and autophagy in lung cancer A549/DDP cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(6): 616-623.
[3]	LIU Yunfan, DU Yuemei, LIU Xiaoyi, GAO Liping. Effects of lycium barbarum polysaccharides on cis-dichlorodiamineplatinum (II)-induced apoptosis in mouse testis sertoli cells TM4#br# [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(6): 624-630.
[4]	SHEN Longde, LI Ailu, LI Lichun, WU Yinyin, SHEN Longyuan, JIANG Qiuxia, HE Jinxi, WU Zhifen, YU Liji, ZHANG Xiaohong. Experimental study on the effect of curcumin on endometriosis in rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(8): 862-868.
[5]	HOU Bin, HUANG Weiping, YIN Zhongpu, HU Shousen. lncRNA PCAT19 inhibits the proliferation and invasion of nasopharyngeal carcinoma cells by adsorbing miR-142-5p and regulating the expression of ING3 gene [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(7): 721-727.
[6]	CHENG Jianping, LI Zhen, ZHAO Xiaolin, YANG Mengyuan, JI Xiwei, YU Jiufei. Research on the expression of miR-186-5p in serum of patients with colon cancer#br# [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(10): 1097-1104.
[7]	TENG Xiaojing, DONG Xueyan, WANG Zhiyi, YU Daojun, WANG Xianjun. Experimental study of Fuzheng Kangfu mixture combined with cisplatin on apoptosis of the gastric cancer cell SGC7901 [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(7): 744-749.
[8]	ZHENG Zhongqiu, XIE Bojian, CUI Binbin, KE Yichen, LIN Yi. miR-106 b expression in breast cancer tissues and mechanism of enhancing cisplatin sensitivity in breast cancer cells [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(5): 541-545.
[9]	QIN Boyu, WANG Gang, QI Xiaoguang, WANG Yajie, SUN Qiong, SUN Shengjie. Inhibitory effect of cisplatin combined with zoledronic acid on the cell proliferation of lung cancer [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(9): 1027-1030.
[10]	LIU Wencheng，TAN Buzhen，ZHAN Xinlu，HU Hui，HUANG Genhua，CAO Qing. Study on the cisplatin-sensitization effect of tripterygium glycosides on cisplatin-resistant human epithelial ovarian cancer cells (SKOV3/DDP) in vitro [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(12): 1364-1370.
[11]	ZHANG Hong, GU Kang-sheng. Clinical observation of ERCC1 protein expression and cisplatin based chemotherapy on advanced esophageal cancer [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(5): 546-551.
[12]	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.
[13]	WU Chun-yan, WANG Wei, CHEN Xin, CHEN Dong-yun, RUI Jing. Efficacy and therapeutic mechanism of recombinant human endostatin on malignant ascites in mice [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(5): 507-511.
[14]	JIN Yi-feng, HE Bei, LIU Dong-hua, WAN Ying. Relationship between ERCC1,Bcl-2 expression and cisplatin intervention in human lung adenocarcinoma cell lines [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(7): 764-768.
[15]	ZHAO Wen-ying, CHEN Dong-yun, CHEN Jing-hua. Observation of short-term therapeutic and adverse effect of lentinan and gemcitabine plus cisplatin as the first-line treatment for advanced non-small cell lung cancer [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(1): 71-77.