Differential gene expression of the inhibitor of apoptosis proteins in docetaxel-resistant gastric cancer cells.
- Author:
Ting-ting WANG
1
;
Jia WEI
;
Xiao-ping QIAN
;
Li-xia YU
;
Bao-rui LIU
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; administration & dosage; pharmacology; Apoptosis; drug effects; Cell Line, Tumor; Cisplatin; pharmacology; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Fluorouracil; pharmacology; Humans; Inhibitor of Apoptosis Proteins; metabolism; Microtubule-Associated Proteins; metabolism; Organoplatinum Compounds; pharmacology; Paclitaxel; pharmacology; Proto-Oncogene Proteins c-bcl-2; metabolism; Stomach Neoplasms; metabolism; pathology; Taxoids; administration & dosage; pharmacology; X-Linked Inhibitor of Apoptosis Protein; metabolism
- From: Chinese Journal of Oncology 2008;30(8):573-577
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVEResistance to chemotherapy may indicate an unfavorable outcome for patients with gastric cancer. The purpose of this study was to examine whether docetaxel-resistance could be due in part to the expression of the inhibitor of apoptosis proteins (IAP).
METHODSDocetaxel-resistant cells, BGC-823/R1, BGC-823/R2 and BGC-823/R3, were established from parent BGC-823 cells by stepwise increasing concentration of docetaxel. To characterize these cells, we examined the effects of docetaxel on cell growth and apoptosis by MTT assay and double staining with both annexin-V-FITC and PI, and analyzed the cross-resistance to various anticancer drugs. Expression of IAP compared with that in parental cells was evaluated by real-time quantitative PCR.
RESULTSThe BGC-823 resistant cells, BGC-823/R1, R2 and R3 cells, were 10.2-, 24.5-, 56.3-fold more resistant to docetaxel than parental cells, respectively, and this resistance was paralleled with reduced induction of apoptosis. BGC-823/R3 cells showed cross-resistance to paclitaxel, whereas exhibited weak or no cross-resistance against 5-fluorouracil, cisplatin and oxaliplatin. The expressions of survivin and XIAP were gradually increased with the extent of docetaxel resistance (r = 0.909, P < 0.001 and r = 0.892, P < 0.001, respectively).
CONCLUSIONIAP may make an important contribution to the resistance to the apoptotic effect of docetaxel in gastric cancer, and could be used as a potential therapeutic target.
