Objective To study the role of capsaicin on improving the sensitivity of cholangiocarcinoma (CCA) cells to 5 fluorouracil(5-FU)and to investigate its molecular mechanism.Methods The MTT and animal experiment were performed to study the effect of capsaicin on the sensitivity of CCA cells to 5-FU,and the q-PCR and Western blot were performed to study its molecular mechanism.Results The effect of 5-FU inhibiting the growth of CCA cells and in vivo was significantly enhanced by capsaicin (60 μmol/L),as well as the apoptosis induced by 5-FU (P ＜ 0.01).In molecular mechanism study,capsaicin down-regulated the expression of beclinl and atg5,but inhibited the 5-FU-induced autophagy of CCA cells.In addition,capsaicin effectively increased the phosphorylation levels of S6 (S235/236) and AKT (S473).Conclusions Capsaicin can promote cell apopto sis and inhibit cell autophagy to improve the sensitivity of CCA cells to 5-FU significantly,which maybe associated with the activation of PI3K/AKT/mTOR pathway in CCA cells.

Sepsis is life-threatening multiple organ failure (MOF) caused by the disorder of body's response to infection. Although it is the main reason of death in intensive care patients, the mechanism of sepsis-induced MOF is still unclear. As an essential organelle of cells, mitochondrial is responsible for many funtions in cells such as energy supply and signal regulation. Recent researches showed that mitochondrial dysfunction may be one of the important reasons of MOF. This review describes the pathophysiological functions of mitochondria and the pathological damage mechanisms of MOF in sepsis, it will provide the therapeutic targets or new ideas for clinical treatment of sepsis.