关键词: 食管癌, TMS1／ASC, Mcl-1, Bax-α, 吉西他滨

Abstract: Objective To investigate the effect of gemcitabine （GEM） on apoptosis and related differential protein expression in esophageal cancer Eca-109 cells and its possible mechanism. Methods The effects of GEM on the proliferation of Eca-109 cells at different concentrations （1， 2， 4， 8， 16 μg／ml） and at different times （12， 24 h） were detected by MTT， and the median inhibitory concentration （IC50） was calculated. Eca-109 cells were treated with 4.26 μg／ml GEM as the treatment group， and the GEM untreated group was also set up. Flow cytometry was used to detect apoptosis in two groups after 24 h. Two groups of proteins were extracted and identified by two-dimensional gel electrophoresis and matrix assisted laser desorption／ionization time of flight mass spectrometry （MALDI-TOF-MS）. The protein types and functions were identified. Western blotting was used to detect the expression of ASC， Mcl-1 and Bax-α protein in two groups after culture for 12 and 24 h. The ultrastructural changes of mitochondria in the two groups were observed by transmission electron microscope. Results GEM inhibited the proliferation of Eca-109 cells in a concentration and time dependent manner. The IC50 of 12 and 24 h were 5.13 μg／ml and 4.26 μg／ml respectively. The differentially expressed proteins of Eca-109 cells induced by GEM were Bax-α， ASC and Mcl-1 respectively. The expression levels of ASC and Bax-α in GEM treated group were higher than those in GEM untreated group after 12 and 24 h， while the expression level of Mcl-1 was opposite. The difference between the two groups was statistically significant （P＜0.01）. Transmission electron microscopy showed that the ultrastructure of mitochondria in GEM treated group changed drastically. Conclusion GEM can inhibit the proliferation and promote apoptosis of esophageal cancer cells， possibly due to the regulation of ASC， Mcl-1 and Bax-α expression by mitochondrial apoptotic pathway.

Key words:

Esophageal cancer；TMS1／ASC；Mcl-1；Bax-α；Gemcitabine ')">"> Esophageal cancer；TMS1／ASC；Mcl-1；Bax-α；Gemcitabine