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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。
Objective To investigate the regulatory effect of p38 / Fas / FasL signaling pathway on amoxicillin-induced apoptosis in esophageal cancer xenografts in nude mice. Methods The model of esophageal carcinoma xenografts in nude mice was established and given for 4 weeks. The tumor nodules were removed and the tumor volume and tumor growth inhibition rate were calculated. The changes of the structure of the xenografts in nude mice were detected by HE staining. The apoptosis rate in the xenografts was detected by FCM. The expressions of p-p38 and Fas were detected by immunohistochemistry and FCM And FasL protein expression changes; RT-PCR detection of xenograft tumor p38mRNA expression changes. Results ① Valdecoxib significantly reduced tumor weight and tumor growth inhibition rate was 45.80%. ② amoxicillin can increase the rate of apoptosis of tumor cells. (3) Amoxicillin can up-regulate the expression of p38mRNA and protein, and at the same time, the expression of Fas and FasL protein increased. ④ The apoptosis rate of tumor tissue was positively correlated with the expression of p-p38, Fas, FasL protein; There was a positive correlation between p-p38 and Fas, FasL protein expression. ⑤ after giving amoxicillin, nude mice gastrointestinal epithelial morphology is not abnormal. Conclusion Activation of p38MAPK signal transduction pathway, which upregulates the expression of Fas / FasL, may be one of the mechanisms of amoxicillin-induced apoptosis in esophageal cancer cells.