摘要
目的:探索泮托拉唑钠(pantoprazole sodium,PPZ)抑制肺癌细胞上皮间质转化和顺铂耐药的分子机制。方法:通过MTT法、划痕修复实验、Transwell实验和Western blot法比较A549细胞与A549/DDP细胞之间的形态、侵袭能力、迁移能力、药物敏感性和蛋白表达差异,观察泮托拉唑钠对A549/DDP细胞的形态、侵袭能力、迁移能力、药物敏感性和蛋白表达的影响。结果:与A549细胞比较,A549/DDP细胞存在高侵袭能力、高迁移能力、对顺铂耐药、具有间质表型和c-Met/AKT/m TOR通路活化等特点,泮托拉唑钠可抑制A549/DDP细胞的侵袭和迁移能力,逆转其耐药及间质表型,抑制c-Met/AKT/m TOR通路的活化。应用c-Met抑制剂SU11274、PI3K抑制剂LY294002和m TOR抑制剂rapamycin处理A549/DDP细胞后的作用与泮托拉唑钠相似。结论:泮托拉唑钠抑制cMet/AKT/m TOR信号通路抑制肺癌细胞侵袭、迁移、上皮间质转化和顺铂耐药。
AIM：To explore the inhibitory effects of pantoprazole sodium on epithelial-mesenchymal transition and cisplatin resistance in lung cancer cells and the underlying mechanism .METHODS： Using MTT method, wound healing assay , Transwell experiment , Western blot , the differences of morphology , invasion ability , migration ability , drug sensitivity and protein expression between A 549/DDP cells and A549 cells were determined .The effect of pantoprazole sodium on morphology , invasion ability , migration ability , drug sensitivity and protein expression in A 549/DDP cells were also observed.RESULTS： Compared with A549 cells, A549/DDP cells had higher invasion and migration abilities , and lower drug sensitivity , exhibited mesenchymal phenotype and activated c-Met/AKT/mTOR pathway .Pantoprazole sodium inhibited the abilities of invasion and migration , and reversed the mesenchymal phenotype , drug resistance and the c-Met/AKT/mTOR pathway activation in A549/DDP cells.Treatment with c-Met inhibitor SU11274, PI3K inhibitor LY294002 and mTOR inhibitor rapamycin had the same effects on A 549/DDP cells as that of pantoprazole sodium .CONCLUSION：Pantoprazole sodium inhibits invasion , migration, epithelial-mesenchymal transition and cisplatin resistance in lung cancer cells by down-regulating c-Met/AKT/mTOR pathways .
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2016年第10期1788-1798,共11页
Chinese Journal of Pathophysiology
基金
南京军区医学科技创新项目(No.14ZD44
No.15MS158)
浙江省科技厅公益性技术应用研究计划(No.2013C33209
No.2014C33277)
杭州市科技发展计划项目(No.20130633B29
No.20140633B40)
关键词
泮托拉唑钠
肺癌
上皮间质转化
耐药
Pantoprazole sodium
Lung cancer
Epithelial-mesenchymal transition
Drug resistance
