c-FLIP is generally expressed in embryonic tissues, but is not expressed in most normal adult tissues, whereas is over-expressed in

the majority of human cancers. It indicates that c-FLIP may associate with the tumorigenesis and progress of most human cancers. Published information regarding the significance of c-FLIP over-expression Tucidinostat research buy in human tumors has only recently begun to accumulate [21–24]. Human HCCs show resistance to apoptosis mediated by several death receptors. c-FLIP is constitutively expressed in human HCC cell lines, and is expressed with a higher positive rate in human HCC tissues than in noncancerous liver tissues. In the present study, positive immunostaining was detected for c-FLIP in 83.72% of human HCC samples, but was absent from normal hepatic tissues. The other authors’ and our studies suggest that c-FLIP may play an important role in human HCCs. For the patients with c-FLIP overexpression, they may have a shorter recurrence-free survival time. Now, RNAi, that can induce highly specific target gene silencing in mammalian cells using siRNA, has selleck compound been a powerful tool in studying the cell function of any gene. c-FLIP expression can be inhibited by RNA interference using siRNAs, evidence from reduced levels

of c-FLIP mRNA and c-FLIP protein[25]. In this study, the c-FLIP-targeted siRNA vectors were designed to specifically silence mafosfamide c-FLIP. Then, the plasmids MLN2238 cost transcript

containing c-FLIP-targeted siRNA and negative siRNA were constructed and transfected into 7721 cells. We found that there were significant differences between 7721/pSuper-Si1 and 7721/pSuper-Neg in c-FLIP expression at both mRNA and protein levels (Figure. 3A, Figure. 3B). The phenomenon that screened positive clone with lower c-FLIP expression indicated that the c-FLIP-targeted siRNA inhibited c-FLIP expression specifically. Some studies reported that siRNA-mediated silencing of c-FLIP induced spontaneous apoptosis in a panel of p53 wild-type, mutant, and null colorectal cancer cell lines [11]. And the anti-apoptotic role of c-FLIP in regulating TRAIL-mediated apoptosis in colon cancer cells was clearly shown using siRNA methodology [26]. Furthermore, c-FLIP down-regulation sensitized colorectal cancer cells to chemotherapy [27]. And, specific silencing of c-FLIPL was sufficient to sensitize MDA435 cells to doxorubicin. Our study showed that c-FLIP gene silencing enhanced doxorubicin-induced HCC cell apoptosis (Figure. 5). These results indicate that c-FLIP may be an important regulator of chemotherapy-induced cell death in human HCC cells. Conclusion The results of the present investigation demonstrated that c-FLIP is frequently expressed in human HCCs, correlated with Edmondson standard. The HCC patients with c-FLIP overexpression may have a shorter recurrence-free survival time.

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