Study on the mechanism of DDP-resistance mediated by phosphate JNK in gastric cancer / 中华胃肠外科杂志
Chinese Journal of Gastrointestinal Surgery
;
(12): 159-162, 2008.
Article
in Chinese
| WPRIM
| ID: wpr-273871
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the mechanism of DDP-resistance in gastric cancer cell line SGC7901/DDP mediated by phosphate(p)-JNK.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>The 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).</p><p><b>CONCLUSION</b>JNK 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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Stomach Neoplasms
/
Signal Transduction
/
Gene Expression Regulation, Neoplastic
/
Cisplatin
/
Apoptosis
/
ATP Binding Cassette Transporter, Subfamily B, Member 1
/
Drug Resistance, Multiple
/
Drug Resistance, Neoplasm
/
Cell Line, Tumor
Limits:
Humans
Language:
Chinese
Journal:
Chinese Journal of Gastrointestinal Surgery
Year:
2008
Type:
Article
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