The Effect and Mechanism of Vinorelbine on Cisplatin Resistance of Human Lung Cancer Cell Line A549/DDP
10.3779/j.issn.1009-3419.2014.02.14
- VernacularTitle:异长春花碱逆转肺癌顺铂耐药A549/DDP细胞耐药性的作用和机制
- Author:
QI CHUNSHENG
1
;
GAO SEN
;
LI HUIQIANG
;
GAO WEIZHEN
Author Information
1. 300070天津，天津医科大学药理学教研室，免疫学教研室; 300020天津，中国医学科学院血液病医院，血液学研究所药剂科
- Keywords:
Vinorelbine;
Lung neoplasms;
Cisplatin resistance
- From:
Chinese Journal of Lung Cancer
2014;(2):148-154
- CountryChina
- Language:Chinese
-
Abstract:
Background and objective Drug resistance is a major obstacle on lung cancer treatment and Vinorel-bine is an effective drug to inhibition of tumor proliferation and metastasis. In this study, we investigated the effect and mecha-nism of Vinorelbine on reversing the cisplatin resistance of human lung cancer A549/DDP cell line. Methods With 1μmol/L and 5μmol/L Vinorelbine treatment, MTS assay was employed to determine the effect of the cisplatin sensitivity of tumor cells, lfow cytometry to determine the apoptosis rate and change of Rh-123 content;Western blot to determine the expression of MDR1, Bcl-2, surviving, PTEN, caspase-3/8 and phosphorylation level of Akt (p-Akt);Real-time PCR was to determine the mRNA expression of MDR1, Bcl-2, survivin and PTEN. Finally the transcriptional activities of NF-κB, Twist and Snail were determined by reporter gene system. Results With 1μmol/L and 5μmol/L Vinorelbine treatment, the sensitivity of cancer cells to cisplatin was increased by 1.91-and 2.54-folds respectively, lfow cytometry showed that the content of Rh-123 was el-evated 1.93-and 2.95-folds and apoptosis rate was increased 2.25-and 3.82-folds, Western blot showed that the expression of multidrug resistance related proteins MDR, Bcl-2 and survivin were downregulated, caspase-3/8 and PTEN was upregulated, phosphorylation of Akt was downregulated as well, real-time assay showed that the mRNA expression of MDR1 was down-regulated 43.5%and 25.8%, Bcl-2 was downregulated 57.3%and 34.1%, survivin was downregulated 37.6%and 12.4%, PTEN was upregulated 183.4%and 154.2%, the transcriptional activities of NF-κB was downregulated 53.2%and 34.5%, Twist was downregulated 61.4%and 33.5%, and Snail was downregulated 57.8%and 18.7%. Conclusion Vinorelbine treatment led to increase of cisplatin sensitivity of A549/DDP cells and the mechanisms included the regulation of PTEN/AKT/NF-κB signal pathway to decreased drug resistance gene expression and increased pro-apoptosis gene expression.
