OVER-EXPRESSION OF C-FLIP AND BCL-2 RESULTS IN THE RESISTANCE TO TRAIL-INDUCED APOPTOSIS ON OVARIAN CANCER

Chen Chen*, Yang Liu**, Xue Yang***, Junqiang Li****, Yan Huang*****, Qin Jiang******, Chunmei Li*******, #

*Department of Intensive Care Unit, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science & Technology of China, Chengdu, Sichuan Province, 610041, China - **Department of Proctology, Chengdu First people's Hospital, No.18 Vientiane North Road, Hi-tech Zone, Chengdu, Sichuan Province, 610041, China- ***Department of Gynecology, West China Fourth University Hospital, Sichuan University, 18 Second People’s South Road, Chengdu, Sichuan Province, 610041, China - ****Department of Obstetrics and Gynecology, the Third people's Hospital of Chengdu, 82 Second the Qinglong Road, Chengdu, Sichuan Province, 610031, China - *****Chengdu Women's & Children's Central Hospital, Chengdu, Sichuan Province, 610031, China - ******Department of Obstetrics and Gynecology, Sichuan Provincial Peoples' Hospital, 32 Second West Section of the First Ring Road, Chengdu, Sichuan Province, 610072, China - *******Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, 610072, China

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumour necrosis factor superfamily of cell death-inducing ligands, which were discovered and cloned by Wiley et al. in the mid-1990s. It has obtained infinite attention as the greatest candidate for cancer therapy because it selectively induces apoptosis in numerous human cancer cells but not in normal cells. However, the development of resistance to TRAIL restricts its utilization in the treatment of ovarian cancer. Here, we showed that B cell lymphoma/lymphoma-2(Bcl-2) and cellular Fas-associated death domain-like interleukin-1 converting enzyme inhibitory protein (c-FLIP), two anti-apoptotic proteins, were over-expressed in a large portion of ovarian cancer tissues, as judged by immunohistochemistry. These proteins may play critical roles as the key points in the regulation of resistance to TRAIL. We hypothesized that downregulation of Bcl-2 and c-FLIP might overcome TRAIL resistance in ovarian cancer cells. The aim of this study was to explore the apoptosis-inducing effects of TRAIL, alone or in combination with Si-Bcl-2 or Si-c-FLIP or both, on OVCA432 ovarian cancer cells.