雷帕霉素对食管鳞癌裸鼠移植瘤生长及mTOR/p70S6K信号通路的影响  

Effects of rapamycin on mTOR/p70S6K signaling pathway and tumor growth in xenografted esophageal squamous cell carcinoma

作　　者：侯桂琴[1,2] 范天黎[3] 王莉莉[4] 陈秀英[1,2] 王俊巍[1,2] 薛乐勋[4] 

机构地区：[1]郑州大学药学院临床药学系,郑州450001 [2]郑州大学新药研究中心,郑州450001 [3]郑州大学基础医学院药理教研室,郑州450001 [4]郑州大学细胞生物研究室,郑州450052

出　　处：《肿瘤》2009年第6期559-562,共4页Tumor

摘　　要：目的:探讨雷帕霉素(rapamycin,RAPA)对荷人食管鳞癌裸鼠移植瘤生长及mTOR/p70S6K信号通路的影响。方法:建立人食管鳞癌细胞株EC9706的裸鼠移植瘤模型,观察经RAPA和RAPA联合顺铂治疗后荷瘤裸鼠的肿瘤生长情况;应用TUNEL、RT-PCR及Western印迹法观察肿瘤组织中的细胞凋亡、mTOR和p70S6K mRNA以及mTOR、p70S6K和p-p70S6K的蛋白表达。结果:RAPA和顺铂均使肿瘤生长速度减慢(P<0.05),并且2者联合应用效果更好(P<0.01);TUNEL检测发现,RAPA在体内能引起EC9706细胞的凋亡(P<0.05);RT-PCR和Western印迹法检测结果表明,RAPA在体内降低了mTOR、p70S6K mRNA和mTOR、p-p70S6K的蛋白表达,但可提高p70S6K的蛋白表达水平。结论:RAPA在体内通过抑制mTOR/p70S6K信号通路的活性促进细胞凋亡,从而抑制人食管鳞癌细胞EC9706裸鼠移植瘤的生长。Objective：The purpose of this study was to investigate the effects of rapamycin （RAPA） on tumor growth and mTOR/p70S6K signaling pathway in xenograft of esophageal squamous cell carcinoma （ESCC） EC9706 cells. Methods： EC9706 cells were subcutaneously inoculated into BALB/c nude mice to establish the xenografted model. And then the tumors were treated with RAPA or RAPA plus eisplatin. The growth of xenografted tumor was observed. Apoptosis of xenografted tumor cells in nude mice was investigated by TUNEL assay. The mRNA expression of roTOR and p70S6K was detected by RT-PCR and the protein expression of mTOR, p70S6K, and p-p70S6K was measured by Western blotting. Results： Both RAPA and eisplatin significantly slowed down the growth speed of xenografted tumors compared with control group （ P 〈 0.05 ） and their combination had a stronger effect than that of RAPA or cisplatin single treatment （P 〈 0.01 ）. The results of TUNEL demonstrated that rapamycin obviously induced apoptosis of EC9706 cells. The results of RT-PCR and Western blotting revealed that rapamycin significantly decreased the expressions of mTOR, p70S6K mRNAs and mTOR, p-p70S6K proteins but increased the expression level of p70S6K protein. Conclusion： RAPA inhibited the mTOR/p70S6K signaling pathway and induced apoptosis of EC9706 cells in vivo, thereby suppressing the growth of xenografted esophageal squamous cell carcinoma EC9706 in nude mice.

关 键 词：食管癌 动物实验 小鼠 裸 雷帕霉素 细胞 EC9706 

分 类 号：R735.1[医药卫生—肿瘤]