Studies on cell death and survival regulatory protein c-FLIP as a target for cancer treatment
10.3969/j.issn.1001-1978.2014.11.004
- VernacularTitle:以细胞存亡调控蛋白c-FLIP为靶点的癌症治疗研究
- Author:
Lili CHEN
;
Zhongming CHEN
;
Guanlin WANG
;
Kwenjen CHANG
- Publication Type:Journal Article
- Keywords:
c-FLIP;
TRAIL;
antiapoptosis;
cancer therapy;
antitumor drug targets;
chemotherapy agents;
selective anti-tumor agents
- From:
Chinese Pharmacological Bulletin
2014;(11):1496-1502
- CountryChina
- Language:Chinese
-
Abstract:
Many tumor cells are resistant to cell apoptosis through the expression of antiapoptotic proteins. c-FLIP is a ma-jor resistance protein of antiapoptosis. In human cells, there are three types of c-FLIP, c-FLIPL , c-FLIPS and c-FLIPR . The c-FLIP binds to FADD to prevent the formation of procaspase-8-DISC and the subsequent activation of caspase cascade. Further-more, c-FLIPL and c-FLIPS have multifunctional roles in various cellular signaling pathways, as well as up-regulating several cyto-protective signaling. Studies show that upregulation of c-FLIP has been found in various tumors, and its downregulation has been shown to restore apoptosis triggered by various chemothera-peutic agents, like the transcriptional regulating agents, trichos-tatin-A, camptothecin, cisplatin, doxorubicin, etc. or other new biotechnologies, such as the specific siRNA. Therefore, c-FLIPS are important targets of cancer therapy. This review summarizes the results on the role of c-FLIP in cancer chemotherapy of tradi-tional antitumor agents and siRNA, and to provide new ideas and rationales of searching for the antiapoptosis effective compounds that can specifically antagonize c-FLIP.
