Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: All-trans retinoic acid inhibits KIT activity and induces apoptosis in gastrointestinal stromal tumor GIST-T1 cell line by affecting on the expression of survivin and Bax protein | Chi et al. Journal of Experimental Clinical Cancer Research 2010 29 165 http content 29 1 165 Journal of Experimental Clinical Cancer Research RESEARCH Open Access All-trans retinoic acid inhibits KIT activity and induces apoptosis in gastrointestinal stromal tumor GIST-T1 cell line by affecting on the expression of survivin and Bax protein 3 2 1 Hoang Thanh Chi 1 Bui Thi Kim Ly 1 Takahiro Taguchi Toshiki Watanabe Yuko Sato Abstract Background Imatinib a selective tyrosine kinase inhibitor has been used as a standard first-line therapy for irresectable and metastasized gastrointestinal stromal tumor GIST patients. Unfortunately most patients responding to imatinib will eventually exhibit imatinib-resistance the cause of which is not fully understood. The serious clinical problem of imatinib-resistance demands alternative therapeutic strategy. This study was conducted to investigate the effect of all-trans retinoic acid ATRA on GIST cell lines. Methods Cell proliferation was determined by trypan blue dye exclusion test. Western blot analysis was performed to test the expression of activated KIT its downstream proteins and apoptosis associated proteins. The cytotoxic interactions of imatinib with ATRA were evaluated using the isobologram of Steel and Peckham. Results and conclusion In this work for the first time we have demonstrated that ATRA affected on cell proliferation of GIST-T1 and GIST-882 cell line through inhibition of cell growth in a dose dependent manner and induced apoptosis. High dose of ATRA induced morphologic change in GIST-T1 cells rounded-up cells and activated the caspase-3 protein. In further examination we found that the ATRA-induced apoptosis in GIST-T1 cells was accompanied by the down-regulated expression of survivin and up-regulated expression of Bax protein. Moreover ATRA suppressed the activity of KIT protein in GIST-T1 cells and its downstream signal AKT activity but not MAPK activity. We also have demonstrated .
