The role of BAG-1 in endoplasmic reticulum stress and the enhancement of cisplatin sensitivity in A549 lung cancer cells induced by tunicamycin
10.3781/j.issn.1000-7431.2012.02.004
- Author:
Jing-Song LIU
1
Author Information
1. Department of Thoracic Surgery
- Publication Type:Journal Article
- Keywords:
Apoptosis;
BAG-1 protein;
Bcl-associated death protein;
Cisplatin;
Endoplasmic reticulum stress;
Lung neoplasms;
Tunicamycin
- From:
Tumor
2012;32(2):99-104
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To observe the induced effect of low dose of tunicamycin on endoplasmic reticulum stress (ERS) of A549 human lung adenocarcinoma cells in vitro and the change of Bcl-2 associated athanogene 1 (BAG-1) protein expression, as well as the changes of cisplatin (DDP) sensitivity and the BAG-1 protein expression. Methods: The expressions of GRP78 (a marker protein in ERS) and BAG-1 proteins in A549 cells treated with low dose of tunicamycin were detected by Western blotting. The change of half inhibitory concentration (IC50) of DDP for A549 cells after pretreatment with tunicamycin was measured by MTT method, and the DDP sensitivity was determined by flow cytometry (FCM). The Western blotting was carried out to detect the expressions of BAG-1 and procaspase-12 proteins in A549 cells induced by DDP after pretreatment with tunicamycin. Results: The ERS in A549 cells could be induced by pretreatment with 1.25 μg/mL tunicamycin for 8 h, which displayed that the expression levels of GRP78 and BAG-1 proteins were both up-regulated (P <0.05). The ERS could increase the DDP sensitivity in the A549 cells (P <0.05). Before ERS occurred, all of three doses of DDP (1.25, 2.5 and 5 μg/mL) could up-regulate the expression level of BAG-1 protein (P <0.05), and this effect was more obvious in 1.25 μg/mL DDP-treated A549 cells. When ERS occurred, the expression levels of BAG-1 protein in all of three doses of DDP (1.25, 2.5 and 5 μg/mL)-treated A549 cells were down-regulated in a dosedependent manner as compared with that in the A549 cells without DDP treatment (P <0.05). The DDP dose of 2.5 and 5 μg/mL could induce apoptosis by ERS pathway, and the expression levels of BAG-1 and procaspase-12 proteins were both down-regulated during this process (P <0.05). Conclusion: BAG-1 may be one of the important regulatory factors in both pathways of ERS- and cisplatin-induced apoptosis of lung cancer cells, and ERS-related apoptotic pathway may be one of the important pathways of cisplatininduced apoptosis of lung cancer cells. Copyright © 2012 by TUMOR.
