Expression and Signiifcance of IKBKB in Pulmonary Adenocarcinoma A549 Cells and Its Cisplatin-resistant Variant A549/DDP
10.3779/j.issn.1009-3419.2014.05.01
- VernacularTitle:IKBKB在人肺腺癌细胞株A549及其耐药细胞株A549/DDP中的表达和意义
- Author:
QI KANG
1
;
LI YANG
;
LI XUEBING
;
ZHANG FANG
;
SHAO YI
;
ZHOU QINGHUA
Author Information
1. 300052天津，天津市肺癌转移与肿瘤微环境重点实验室，天津市肺癌研究所，天津医科大学总医院
- Keywords:
IKBKB;
NF-κB;
Drug-resistant;
Lung neoplasms
- From:
Chinese Journal of Lung Cancer
2014;(5):363-368
- CountryChina
- Language:Chinese
-
Abstract:
Background and objective Cisplatin-resistance in Lung cancer cells is widespread in the clinical treat-ment, seriously affecting the effects of the treatment of lung cancer. hTerefore, the research of mechanisms of cisplain-resistance has significant meaning for developing new chemotherapeutic drug and solving the cisplain-resistance in clinic treatment. IKBKB is one of the most important catalytic subunits of IKK complexes. It plays an important regulatory role in activation of NF-κB. hTe aim of this study is to investigate the differential expression of IKBKB gene in human lung adenocarcinoma cells line A549 and the cisplatin-resistant variant A549/DDP and the mechanisms of cisplain-resistance induced by IKBKB gene. Methods MTT assay was employed to determine the sensitivity of A549 and A549/DDP cells line to cisplatin and the effect of IKBKB gene on A549 cell lines’ sensitivity to cisplatin. hTe mRNA level of IKBKB was determined by real-time PCR. Dual luciferase reporter gene experiment was employed to determine the activity of the NF-κB. Apoptosis rate of lung adenocarci-noma cells was determined by lfow cytometry. Results Apoptosis rate and IC50 were signiifcantly different in A549 and A549/DDP cells, the expression of mRNA level of IKBKB gene in A549/DDP was signiifcantly higher than that in A549. Compared with control group, IKBKB gene was able to reduce the cisplain sensitivity of A549 cells. Atfer A549 was transfected with pcD-NA3.1/IKBKB plasmid, mRNA level of IKBKB was signiifcantly increased, the sensitivity of cisplain was decreased, the IC50 was increased 2.85 fold, the apoptosis rate was decreased 59%, the activity of NF-κB has been greatly increased. Conclusion IKBKB inhibits cisplatin-induced apoptosis via the activation of NF-κB pathway. It will be helpful in the development of new anticancer drug and solving the challenge of cisplatin-resistance.
