[1]王浩,李维,谭国林.长片段非编码RNA XIST可改变人鼻咽癌HNE1 细胞对顺铂的耐药性[J].南方医科大学学报,2019,(03):357.[doi:10.12122/j.issn.1673-4254.2019.03.15]
点击复制

长片段非编码RNA XIST可改变人鼻咽癌HNE1 细胞对顺铂的耐药性()
分享到:

《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2019年03期
页码:
357
栏目:
出版日期:
2019-04-11

文章信息/Info

Title:
Long non-coding RNA XIST modulates cisplatin resistance by altering PDCD4 and Fas-L expressions in human nasopharyngeal carcinoma HNE1 cells in vitro
作者:
王浩李维谭国林
关键词:
X失活特异性转录本顺铂人鼻咽癌顺铂耐药HNE1细胞株耐药性蛋白
Keywords:
X inactive specific transcript cisplatin nasopharyngeal carcinoma drug resistance programmed cell death 4 Fas ligand
DOI:
10.12122/j.issn.1673-4254.2019.03.15
摘要:
目的明确长片段非编码RNA(lncRNA)X失活特异性转录本(XIST)对人鼻咽癌细胞顺铂(DDP)耐药性的影响及可能的 机制。方法通过荧光定量PCR检测人鼻咽癌顺铂耐药HNE1细胞株(HNE1/DDP)中XIST的表达特征。采用MTT试验观察 XIST上调和下调对HNE1/DDP细胞DDP耐药性的影响,并通过EdU试验和流式细胞技术观察其对HNE1/DDP细胞增殖和凋 亡的影响。采用蛋白质印迹法检测XIST上调和下调对促凋亡因子程序性细胞死亡4(PDCD4)和Fas配体(Fas-L)蛋白表达的 影响。结果XIST在HNE1/DDP细胞的表达量显著高于HNE1细胞(0.57±0.06 vs 0.1±0.02,P<0.05)。下调XIST的表达显著降 低HNE1/DDP 细胞对DDP 的耐药性(P<0.05),而上调XIST 增加对DDP 的耐药性(P<0.05)。下调XIST 的表达显著降低 HNE1/DDP细胞增殖(6.17±1.93 vs 16.59 4.86, P<0.05)并诱导细胞凋亡[(18.04±4.72)% vs(4.22±1.65)%, P<0.05],而上调XIST 增加细胞增殖(25.40±7.21 vs 13.16±3.95, P<0.05)并抑制细胞凋亡[(2.82±0.88)% vs(6.46±1.75)%, P<0.05]。下调XIST的表达 显著增加HNE1/DDP细胞中PDCD4(4.10±0.42 vs 1.0±0.12, P<0.05和Fas-L(3.07 0.29 vs 1.0±0.14, P<0.05)蛋白的表达,而上调 XIST降低PDCD4(0.36±0.11 vs 1.0±0.18, P<0.05)和Fas-L(0.17±0.09 vs 1.0±0.21, P<0.05)蛋白的表达。结论XIST在HNE1/ DDP细胞中表达升高,下调和上调XIST的表达可分别降低和增加HNE1/DDP细胞对DDP的耐药性,其机制可能与PDCD4和 Fas-L蛋白表达改变相关。
Abstract:
Objective To explore the role of long non-coding RNA (lncRNA) X inactive specific transcript (XIST) in modulating cisplatin (DDP) resistance of human nasopharyngeal carcinoma cells and investigate the possible mechanism. Methods Realtime PCR was performed to detect the expression of XIST in cisplatin-resistant human nasopharyngeal carcinoma cell line HNE1/DDP. The effects of up-regulation and down-regulation of XIST on DDP resistance, proliferation and apoptosis of HNE1/ DDP cells were assessed using MTT assay, EdU assay and flow cytometry. Western blotting was used to detect the changes in the expressions of programmed cell death 4 (PDCD4) and Fas ligand (Fas-L) proteins in the cells in response to up-regulation or down-regulation of XIST. Results The expression of XIST was significantly up-regulated in HNE1/DDP cells in comparison with HNE1 cells (0.57±0.06 vs 0.1±0.02, P<0.05). Down-regulation of XIST significantly decreased while up-regulation of XIST obviously increased DDP resistance of HNE1/DDP cells (P<0.05). Down-regulation of XIST significantly reduced the proliferation (6.17 ± 1.93 vs 16.59 ± 4.86, P<0.05) and enhanced apoptosis [(18.04 ± 4.72)% vs (4.22 ± 1.65)% , P<0.05], while upregulating XIST enhanced the proliferation (25.40±7.21 vs 13.16±3.95, P<0.05) and inhibited apoptosis [(2.82±0.88)% vs (6.46± 1.75)%, P<0.05] in HNE1/DDP cells. Down-regulation of XIST significantly increased the protein expressions of PDCD4 and Fas-L (P<0.05) in HNE1/DDP cells, and up-regulation of XIST resulted in reverse changes in PDCD4 and Fas-L expressions (P< 0.05). Conclusion XIST is up-regulated in HNE1/DDP cells, and down-regulation and up-regulation of XIST expression reduce and increase DDP resistance of the cells, respectively, possibly as a result of changes in the expressions of PDCD4 and Fas-L.

相似文献/References:

[1]余乐,陈明辉,古春萍,等.顺铂下调铜离子转运蛋白1诱导人食管鳞癌细胞EC109耐药[J].南方医科大学学报,2011,(05):801.
[2]陈斯泽,陈雪梅,丁颖,等.Combined chemotherapy with cisplatin, docetaxel and capecitabine for metastatic nasopharyngeal carcinoma:a retrospective analysis[J].南方医科大学学报,2011,(07):1114.
[3]林晓丹,石兴源,周同冲,等.调强或三维适形放疗联合TP 方案化疗治疗局部中晚期食管癌的临床研究[J].南方医科大学学报,2011,(07):1264.
[4]彭萍,吴璇,关婷,等.1-磷酸-神经鞘氨醇干预化疗对荷瘤小鼠卵巢功能和抑瘤效果的影响[J].南方医科大学学报,2012,(03):383.
[5]卢金利,杨芳.宫颈癌中顺铂放疗增敏的临床药代动力学机制[J].南方医科大学学报,2006,(08):1170.
 LU Jin-li,YANG Fang Department of Radiotherapy,First Hospital,et al.Clinical pharmacokinetic study of cisplatin in enhancing cervical cancer radiosensitivity[J].Journal of Southern Medical University,2006,(03):1170.
[6]曹漫明,张积仁,汪森明,等.卵巢癌顺铂耐药细胞中DNA转录与修复相关基因的表达[J].南方医科大学学报,2005,(12):1478.
 CAO Man-ming,ZHANG Ji-ren,WANG Sen-ming,et al.Expression of DNA transcription-and repair-related genes in cisplatin-resistant human ovarian carcinoma cell line COC1/DDP[J].Journal of Southern Medical University,2005,(03):1478.
[7]杨义明,张水兰,宋华勇,等.TP方案治疗难治性晚期食管鳞癌的临床观察[J].南方医科大学学报,2004,(09):1042.
 YANG Yi-ming,ZHANG Shui-lan,SONG Hua-yong,et al.Clinical observation of TP regiment for treating refractory and terminal squamous cancer of the esophagus[J].Journal of Southern Medical University,2004,(03):1042.
[8]冯正富,潘辉林,宋慧胜,等.同期放化疗治疗中晚期鼻咽癌临床研究[J].南方医科大学学报,2004,(06):694.
 FENG Zheng-fu,PAN Hui-lin,SONG Hui-sheng,et al.Radiotherapy with concurrent chemotherapy for treatment of advanced nasopharyngeal carcinoma[J].Journal of Southern Medical University,2004,(03):694.
[9]宋乐乐,马琳艳,张旭东,等.衣霉素联合顺铂对人鼻咽癌细胞增殖和凋亡的影响[J].南方医科大学学报,2012,(06):766.
[10]兰曦,王勇,曹姝,等.RNA干扰抑制CD133 表达对CD133+肝癌干细胞增殖和化疗敏感性的影响[J].南方医科大学学报,2012,(12):1741.

更新日期/Last Update: 1900-01-01