Li Da-Wei, Peng Zhi-Hai, Li Zhen-Zhen, Zhang Yan-Hong, Zhao Mian-Zhi, Wu Qing
Department of General Surgery, The First People's Hospital of Shanghai, Shanghai Jiaotong University, Shanghai 200080, China.
Zhonghua Wei Chang Wai Ke Za Zhi. 2008 Mar;11(2):159-62.
To investigate the mechanism of DDP-resistance in gastric cancer cell line SGC7901/DDP mediated by phosphate(p)-JNK.
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.
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).
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.
探讨磷酸化（p）-JNK介导胃癌细胞系SGC7901/DDP顺铂耐药的机制。
采用JNK抑制剂SP600125阻断p-JNK表达。通过MTT法检测药物敏感性。采用流式细胞术检测细胞凋亡率。通过蛋白质印迹法检测p-JNK和P-糖蛋白（P-gp）的表达。采用免疫组化SP法在包含168个癌组织斑点和27个正常胃组织斑点的组织芯片中检测两种蛋白的表达。采用Pearson法分析p-JNK与P-gp之间的相关性。
在SGC7901细胞（p-JNK：1.17±0.03 vs 0.38±0.071，P-gp：0.21±0.01 vs 0.06±0.01）和SGC7901/DDP细胞（p-JNK：2.56±0.14 vs 1.02±0.12，P-gp：0.77±0.05 vs 0.52±0.06）中，SP600125抑制p-JNK后，药物敏感性和细胞凋亡率显著升高（P<0.01），p-JNK和P-糖蛋白的蛋白表达水平下调（均P<0.01）。胃癌组织中p-JNK和P-糖蛋白的蛋白表达率分别为45.8%和51.8%，显著高于正常胃组织中的7.4%和18.5%（P<0.01）。p-JNK与P-gp蛋白表达呈正相关（P<0.01）。
JNK抗凋亡通路通过调节P-gp表达在胃癌顺铂耐药中起重要作用，可能是逆转多药耐药的新靶点。
