p38/Fas/FasL在戊地昔布诱导食管癌裸鼠移植瘤细胞凋亡中的调控作用  

Regulatory effect of p38/Fas/FasL on the apoptosis of cancer in nude mice induced by valdecoxib

作　　者：张玉军[1] 刘淑霞[1] 刘青娟[1] 左连富[2] 刘俊茹[1] 郭建文[2] 吴海江[1] 王晓月[3] 

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 [3]中国电子科技集团公司第五十四所职工医院,河北石家庄050081

出　　处：《中国药理学通报》2009年第8期1081-1085,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p38/Fas/FasL信号途径在戊地昔布诱导裸鼠食管癌移植瘤细胞凋亡中的调控作用。方法建立食管癌裸鼠移植瘤模型,给予戊地昔布4 wk。剥离瘤结节,计算瘤体体积和肿瘤生长抑制率;HE染色检测裸鼠移植瘤的结构变化;FCM法检测移植瘤中的细胞凋亡率;免疫组织化学和FCM法检测p-p38、Fas和FasL蛋白的表达变化;RT-PCR检测移植瘤中p38mRNA表达变化。结果①戊地昔布可明显降低肿瘤重量,肿瘤生长抑制率为45.80%。②戊地昔布可增加肿瘤细胞的凋亡率。③戊地昔布可上调p38mRNA和蛋白的表达;同时凋亡基因Fas和FasL蛋白表达升高。④肿瘤组织的凋亡率与p-p38、Fas、FasL蛋白表达呈正相关;p-p38与凋亡基因Fas、FasL蛋白表达之间均呈正相关。⑤给予戊地昔布后,裸鼠胃肠上皮细胞形态没有异常。结论激活p38MAPK信号转导途径,从而上调凋亡相关基因Fas/FasL的表达,可能是戊地昔布诱导食管癌细胞凋亡的机制之一。Aim To investigate the regulatory effect of p38/Fas/FasL signal pathway on the apoptosis of cancer in nude mice induced by valdecoxib. Methods The tumor model was established by inoculating 2×10^6 cell both in the left and fight armpits respectively. The mice were divided randomly into control group and valdeeoxib group （20 mg·kg^-1·day^-1 ）. Valdecoxib was dissolved in carboxymethylcellulose sodium and administrated from the second day after inoculation. The mice were killed after 4 weeks. The volume and inhibitory rate were calculated according to the length and width of xenograft tumor. H. E staining was used to observe pathological change of the tumor, stomach and colon. The apoptotic rate was detected by FCM. The expressions of p-p38, Fas and FasL protein were detected with FCM and immunohistochemical staining. Total RNA was extracted with Trizol method and the expression of p38 mRNA was detected by RT-PCR. Restilts ①Valdeeoxib inhibited the growth of tumor. The weight of tumor was decreased from （1.43 ±0. 52）g in control group to （0. 93±0. 53 ）g in valdecoxib treated group. The ratio of inhibition on the growth of tumor was 45.80%. ②Valdecoxib increased the apoptosis rate from （14. 15±0. 48 ）% in control group to （ 29.80± 6. 35 ） % in treated group. ③RT- PCR showed that the expression of p38MAPK mRNA increased in treated group compared with that in control group. FCM and immunohistochemical staining showed that the expressions of p-p38MAPK, Fas and FasL were increased in valdecoxib treated group. There was statistical significance compared with control group.④There was significantly positive correlation between the ratio of apoptosis and the expressions of p-p38, Fas and FasL protein respectively （ r = 0. 603, 0. 812,0. 813 ;P =0. 038,0. 001,0. 001 ） ; The expression of p38 protein was positively correlated with Fas and FasL protein respectively （ r = 0. 697,0. 762 ; P = 0. 012, 0. 00d ）. ⑤Valdecoxib did not affect cell structures of stomach and colon. Conclusion

关 键 词：戊地昔布 裸鼠 食管癌 凋亡 p38MAPK FaL FASL 

分 类 号：R-332[医药卫生] R329.25