[1]毛楠,何关生,饶进军,等.沉默Bmi-1表达可逆转肺癌细胞对顺铂的耐药性[J].南方医科大学学报,2014,(07):1000.
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沉默Bmi-1表达可逆转肺癌细胞对顺铂的耐药性()
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《南方医科大学学报》[ISSN:/CN:]

卷:
期数:
2014年07期
页码:
1000
栏目:
出版日期:
2014-07-15

文章信息/Info

Title:
Effect of silencing Bmi-1 expression in reversing cisplatin resistance in lung cancer cells
and its mechanism
作者:
毛楠何关生饶进军吕琳
关键词:
肺肿瘤顺铂耐药性Bmi-1衰老细胞周期
Keywords:
lung neoplasm cisplatin drug-resistance Bmi-1 cell senescence cell cycle
摘要:
目的探讨沉默Bmi-1表达在逆转人肺癌顺铂耐药性的作用及机制。方法以siRNA沉默Bmi-1表达,MTT法检测细胞
顺铂敏感性,流式细胞术检测细胞周期分布与凋亡,β-半乳糖酐酶染色法检测细胞的衰老,Western blot法检测Bmi-1、P14ARF、
P16INK4a、P53、P21、Rb、ubi-H2AK119蛋白表达。结果肺癌顺铂耐药株A549/DDP细胞的Bmi-1表达明显高于A549细胞;沉默
Bmi-1的表达显著增加耐药株对顺铂的敏感性(IC50从40.3±4.1 μmol/L降到18.3±2.8 μmol/L,P<0.01),细胞G0/G1期比值显著升
高[从(48.9±2.3)%升到(78.7±7.6)%,P<0.01];细胞β-半乳糖酐酶染色阳性,呈衰老特征。细胞衰老通路的P14ARF、P16INK4a、P53、
P21、Rb表达上调,ubi-H2AK119表达下调。结论沉默Bmi-1表达能诱导A549/DDP细胞衰老,逆转对顺铂的耐药性,其作用
机制可能与降低ubi-H2AK119表达、调节INK4a/ARF/Rb衰老通路有关。
Abstract:
Objective To investigate the effect of silencing Bmi-1 expression in reversing cisplatin resistance in human lung
cancer cells and explore the possible mechanisms. Methods Cisplatin-resistant A549/DDP cells with small interference RNA
(siRNA)-mediated Bmi-1 expression silencing were examined for cisplatin sensitivity using MTT assay and alterations in cell
cycle distribution and apoptosis with flow cytometry, and the changes in cell senescence was assessed using β-galactosidase
staining. The protein expressions of Bmi-1, P14ARF, P16INK4a, P53, P21, Rb and ubi-H2AK119 in the cells were determined with
Western blotting. Results A549/DDP cells showed significantly higher Bmi-1 expression than A549 cells. After
siRNA-mediated Bmi-1 silencing, A549/DDP cells showed significantly enhanced cisplatin sensitivity with an increased IC50
from 40.3±4.1 μmol/L to 18.3±2.8 μmol/L (P<0.01) and increased cell percentage in G0/G1 phase from (48.9±2.3)% to (78.7±7.6)%
(P<0.01). Silencing Bmi-1 did not cause significant changes in the cell apoptosis rate but induced obvious senescence
phenotype in A549/DDP cells with down-regulated expression of ubi-H2AK119 and up-regulated expressions of P14ARF,
P16INK4a, P53,P21 and Rb. Conclusion Silencing Bmi-1 by RNA interference can induce cell senescence and resensitize A549/
DDP cells to cisplatin possibly by regulating INK4a/ARF/Rb senescence pathway.

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更新日期/Last Update: 1900-01-01