Study on the mechanism of DDP-resistance mediated by phosphate JNK in gastric cancer.
- Author:
Da-Wei LI
1
;
Zhi-Hai PENG
;
Zhen-Zhen LI
;
Yan-Hong ZHANG
;
Mian-Zhi ZHAO
;
Qing WU
Author Information
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette, Sub-Family B, Member 1; metabolism; Apoptosis; drug effects; Cell Line, Tumor; Cisplatin; metabolism; pharmacology; Drug Resistance, Multiple; drug effects; Drug Resistance, Neoplasm; drug effects; Gene Expression Regulation, Neoplastic; Humans; JNK Mitogen-Activated Protein Kinases; metabolism; Signal Transduction; Stomach Neoplasms; drug therapy; metabolism
- From: Chinese Journal of Gastrointestinal Surgery 2008;11(2):159-162
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the mechanism of DDP-resistance in gastric cancer cell line SGC7901/DDP mediated by phosphate(p)-JNK.
METHODSThe p-JNK expression was blocked by the JNK inhibitor SP600125. The drug sensitivity was detected by MTT. Cell apoptosis rate was measured by flow cytometry. The expression of p-JNK and P-glycoprotein (P-gp) was examined by Western blot. The expression of both proteins were detected in a tissue microarray containing 168 spots of cancer tissue and 27 spots of normal gastric tissue by SP immunohistochemistry. Pearson method was used to analyze the correlation between p-JNK and P-gp.
RESULTSThe drug sensitivity and cell apoptosis rate significantly increased (P<0.01), and the protein expression levels of p-JNK and P-glycoprotein were down-regulated after the inhibition of p-JNK by SP600125 in both SGC7901(p-JNK: 1.17+/-0.03 vs 0.38+/-0.071, P-gp: 0.21+/-0.01 vs 0.06+/-0.01) and SGC7901/DDP (p-JNK: 2.56+/-0.14 vs 1.02+/-0.12, P-gp: 0.77+/-0.05 vs 0.52+/-0.06 )cells(all P<0.01). The protein expression rates of p-JNK and P-glycoprotein were 45.8% and 51.8% respectively in gastric cancer tissue, which were significantly higher than those in normal gastric tissue 7.4% and 18.5% (P<0.01). The correlation of protein expression of p-JNK and P-gp was positive (P<0.01).
CONCLUSIONJNK anti-apoptosis pathway with the regulation of P-gp expression plays an important role in the DDP-resistance of gastric cancer, which may be a novel target for reversing multidrug resistance.
