Considering the results of our previous research that conjugated linoleic acid mixture-paclitaxel （CLA-mixture-PTX） possesses anti-tumor activity against melanoma and brain glioma, the purpose of this study was to i...Considering the results of our previous research that conjugated linoleic acid mixture-paclitaxel （CLA-mixture-PTX） possesses anti-tumor activity against melanoma and brain glioma, the purpose of this study was to investigate the potential anti-tumor efficacy of cis-9, trans- 1 1-conjugated linoleic acid-paclitaxel （c9, tl 1-CLA-PTX） and trans- 1 O, cis- 12-conjugated linoleic acid-paclitaxel （tl0, c12-CLA-PTX） on MCF-7 breast cancer cell line in vitro and in vivo. The in vitro cytotoxicity, apoptosis induction effect and cell cycle arresting effect of c9, t1 1-CLA-PTX and t10, c12-CLA-PTX were investigated. The in vitro cellular uptake of c9, tl 1-CLA-PTX and tl0, cl2-CLA-PTX in MCF-7 cells were also analyzed. Besides, the anti-tumor activity of c9, tl 1-CLA-PTX and tl0, cl2-CLA-PTX was evaluated in MCF-7 tumor bearing nude mice in vivo. The in vitro cytotoxicity results showed that the value of ICs0 of the tl 0, c l2-CLA-PTX is （0.17±0.02） μM, compared with that of （1.08±0.15） μM in CLA-mixture-PTX and （6.50±1.20） μM in c9, tl 1-CLA-PTX treatment group （P〈0.01）. Both tl0, cl2-CLA-PTX and c9, t l 1-CLA-PTX increased the percentage of total apoptotic cells compared with that of control （P〈0.01）. And the rank of apoptosis induction efficacy was t 10, c 12-CLA-PTX〉CLA-mixture-PTX〉c9, t 11-CLA-PTX （P〈0.01）. Compared with untreated cells, the tl0, c12-CLA-PTX and c9, tl 1-CLA-PTX arrested cell cycle progression at the S and G2-M phase. The amount of cellular uptake of t 10, c 12-CLA-PTX was significantly higher than that of CLA-mixture-PTX （P〈0.01）, which was significantly higher than that of c9, t1 1-CLA-PTX （P〈0.01）. The rank of in vivo anti-tumor activity was tl0, c12-CLA-PTX〉CLA-mixture-PTX〉 c9, t1 1-CLA-PTX （P〈0.01）. In conclusion, our study demonstrated that both tl0, cl2-CLA-PTX and c9, tl 1-CLA-PTX has significant anti-tumor activity in MCF-7 cell line. And while c9, tl 1-CLA-PTX showed weaker inhibitory effect than CLA-mixture-PTX, stronger inhibitory effect was presented by t10, c12-CLA-PTX, which could be a promising alternative for CLA-mixture-PTX.展开更多
Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important ro...Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed.展开更多
基金National Natural Science Foundation of China (Grant No.81172992)the National Basic Research Program of China (973 Program,Grant No.2013CB932501)Innovation Team of Ministry of Education (Grant No.BMU20110263)
文摘Considering the results of our previous research that conjugated linoleic acid mixture-paclitaxel （CLA-mixture-PTX） possesses anti-tumor activity against melanoma and brain glioma, the purpose of this study was to investigate the potential anti-tumor efficacy of cis-9, trans- 1 1-conjugated linoleic acid-paclitaxel （c9, tl 1-CLA-PTX） and trans- 1 O, cis- 12-conjugated linoleic acid-paclitaxel （tl0, c12-CLA-PTX） on MCF-7 breast cancer cell line in vitro and in vivo. The in vitro cytotoxicity, apoptosis induction effect and cell cycle arresting effect of c9, t1 1-CLA-PTX and t10, c12-CLA-PTX were investigated. The in vitro cellular uptake of c9, tl 1-CLA-PTX and tl0, cl2-CLA-PTX in MCF-7 cells were also analyzed. Besides, the anti-tumor activity of c9, tl 1-CLA-PTX and tl0, cl2-CLA-PTX was evaluated in MCF-7 tumor bearing nude mice in vivo. The in vitro cytotoxicity results showed that the value of ICs0 of the tl 0, c l2-CLA-PTX is （0.17±0.02） μM, compared with that of （1.08±0.15） μM in CLA-mixture-PTX and （6.50±1.20） μM in c9, tl 1-CLA-PTX treatment group （P〈0.01）. Both tl0, cl2-CLA-PTX and c9, t l 1-CLA-PTX increased the percentage of total apoptotic cells compared with that of control （P〈0.01）. And the rank of apoptosis induction efficacy was t 10, c 12-CLA-PTX〉CLA-mixture-PTX〉c9, t 11-CLA-PTX （P〈0.01）. Compared with untreated cells, the tl0, c12-CLA-PTX and c9, tl 1-CLA-PTX arrested cell cycle progression at the S and G2-M phase. The amount of cellular uptake of t 10, c 12-CLA-PTX was significantly higher than that of CLA-mixture-PTX （P〈0.01）, which was significantly higher than that of c9, t1 1-CLA-PTX （P〈0.01）. The rank of in vivo anti-tumor activity was tl0, c12-CLA-PTX〉CLA-mixture-PTX〉 c9, t1 1-CLA-PTX （P〈0.01）. In conclusion, our study demonstrated that both tl0, cl2-CLA-PTX and c9, tl 1-CLA-PTX has significant anti-tumor activity in MCF-7 cell line. And while c9, tl 1-CLA-PTX showed weaker inhibitory effect than CLA-mixture-PTX, stronger inhibitory effect was presented by t10, c12-CLA-PTX, which could be a promising alternative for CLA-mixture-PTX.
基金Supported by NIH KO8 DK093578CCFA Career Development Award 3467(DQS)F Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute
文摘Inflammatory bowel disease (IBD) results from a complex series of interactions between susceptibility genes, the environment, and the immune system. The host microbiome, as well as viruses and fungi, play important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system. New technologies have allowed researchers to be able to quantify the various components of the microbiome, which will allow for future developments in the etiology of IBD. Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells, innate lymphoid cells, cells of the innate (macrophages/monocytes, neutrophils, and dendritic cells) and adaptive (T-cells and B-cells) immune system, and their secreted mediators (cytokines and chemokines). Either a mucosal susceptibility or defect in sampling of gut luminal antigen, possibly through the process of autophagy, leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity. The antigen presenting cells then mediate the differentiation of naïve T-cells into effector T helper (Th) cells, including Th1, Th2, and Th17, which alter gut homeostasis and lead to IBD. In this review, the effects of these components in the immunopathogenesis of IBD will be discussed.
