PDCD4增强鼻咽癌细胞系CNE1对顺铂化疗敏感性机制研究
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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。
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.
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.
引文
[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].
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[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.
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[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 TWISTenhances the cytotoxicity of chemotherapeutic drugs in doxorubicin-resistant Hep G2 cells by suppressing MDR1 and EMT[J].Int J Oncol,2018,53(4):1763-1773.
[2]Asangani IA,Rasheed SA,Nikolova DA,et al.MicroR-NA-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 TWISTenhances the cytotoxicity of chemotherapeutic drugs in doxorubicin-resistant Hep G2 cells by suppressing MDR1 and EMT[J].Int J Oncol,2018,53(4):1763-1773.