p38MAPK在戊地昔布诱导Eca109细胞凋亡中的调控作用  

Regulatory effect of p38MAPK signal pathway on the apoptosis of human esophageal cancer cells induced by valdecoxib

作　　者：张玉军[1] 郝军[1] 刘淑霞[1] 左连富[2] 刘俊茹[1] 吴海江[1] 郭建文[2] 

机构地区：[1]河北医科大学病理学教研室,河北石家庄050017 [2]河北省肿瘤研究所,河北石家庄050011

出　　处：《中国药理学通报》2009年第4期497-501,共5页Chinese Pharmacological Bulletin

基　　金：河北省自然科学基金资助项目(No301354)

摘　　要：目的探讨p38MAPK信号转导途径在戊地昔布诱导食管癌Eca109细胞凋亡中的调控作用。方法将正常培养的人食管癌Eca109细胞随机分为正常对照组、戊地昔布组和戊地昔布+SB203580组;采用流式细胞术和DNA Ladder检测凋亡情况;RT-PCR检测p38mRNA的表达变化;流式细胞术和免疫细胞化学检测p38蛋白的表达变化。结果①戊地昔布能够诱导Eca109细胞发生凋亡,并呈剂量依赖性,而SB203580能够部分降低戊地昔布诱导的Eca109细胞的凋亡率;②戊地昔布能够上调Eca109细胞中p38mRNA和蛋白的表达,而戊地昔布+SB203580组p38mRNA和蛋白的表达下降;③p38蛋白表达与凋亡率呈正相关。结论戊地昔布能够通过部分激活p38MAPK信号途径诱导Eca109细胞发生凋亡。Aim To investigate the regulatory effect of p38MAPK signal pathway on the apoptosis of human e-sophageal cancer cells induced by valdecoxib. Methods The tumor cells were inoculated in the dose of 1 ×10^7 · L^-1. After 6 h, the cells were divided into control group, solution group, 400,200,100,50,25 μmol · L^-1 valdecoxib group and various concentration valdecoxib ＋ SB203580 group, cultured for 72 h. FCM and DNA Ladder were used to detect the apoptosis of Ecal09 cells, p38 mRNA expression was detected by RT-PCR. The expression of p-p38MAPK protein was detected by immunohistochemical staining and FCM. Results ① Valdecoxib could increased the apoptosis rate of Eca109 cell in concentration-dependent fashion. Apoptosis rate was increased to 48.46% in 400 μmol · L^-1 valdecoxib group at the incubation time of 72 h. DNA ladder was the most recognized marker of apopto- sis, and there was obvious DNA ladder in valdecoxib treated group, especially in 400 μmol · L^-1 group. ② Valdecoxib could increase the expression of p38MAPK, while SB203580 could inhibit the over-expression induced by valdecoxib, at the same time, the apoptosis rate was been decreased. ③ The expression of p38MAPK protein was positively correlated with the apoptotic rate （ r = 0. 822, P = 0. 000 ）. Conclusions Valdecoxib could activate p38MAPK pathway, thus induce the apoptosis of Eca109 cells, which may be one of the mechanisms for the inhibition of cell growth by valdecoxib.

关 键 词：人食管癌Eca109细胞 戊地昔布 凋亡 P38MAPK SB203580 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学] R341[医药卫生—基础医学]