TY - JOUR AB - Tumor necrosis factor‑related apoptosis inducing ligand (TRAIL)‑mediated apoptosis is a safe method for the treatment of various types of cancer. However, TRAIL therapy is less effective in certain types of cancer, including cervical cancer. To address this problem, a combinatorial approach was employed to sensitize cervical cancer at low dosages. YM155, a survivin inhibitor, was used at low dosages along with TRAIL to induce apoptosis in HeLa cells. The effects of the individual treatment with TRAIL and YM155 on apoptosis were assessed by propidium iodide assay. In addition, to validate the DNA damage exhibited by the combination treatment, the phosphorylation status of γH2A histone family member X was investigated by immunofluorescence and western blot analysis. TRAIL or YM155 alone had no significant effect on DNA damage and apoptosis. However, the TRAIL/YM155 combination triggered a synergistic pro‑apoptotic stimulus in HeLa cells. The mRNA and protein levels of CASP8‑ and FADD‑like apoptosis regulator (cFLIP), death receptor 5 (DR5) and survivin were monitored using RT‑PCR and western blot analysis, respectively. This combinatorial approach downregulated both mRNA and protein expression levels of cFLIP and survivin. Further experimental results suggested that the combination treatment significantly reduced cell viability, invasion and migration of HeLa cells. Overall, the present findings indicated that the low dosage of YM155 sensitized HeLa cells to TRAIL‑induced apoptosis via a mechanism involving downregulation of cFLIP and survivin. The results indicated the importance of combination drug treatment and reveal an effective therapeutic alternative for TRAIL therapy in human cervical cancer. AD - Graduate School of Biomedical Science and Engineering, Department of Biomedical Science, Hanyang University, Seoul 04763, Republic of Korea Biomedical Research Center, Asan Institute for Life Sciences, Seoul 05505, Republic of Korea Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea AU - Chandrasekaran,Arun,Pandian AU - Poondla,Naresh AU - Ko,Na,Re AU - Oh,Seung,Jun AU - Ramakrishna,Suresh DA - 2020/10/01 DO - 10.3892/ol.2020.11933 IS - 4 JO - Oncol Lett KW - tumor necrosis factor‑related apoptosis inducing ligand therapy YM155 HeLa cells apoptosis CASP8‑ and FADD‑like apoptosis regulator death receptor 5 survivin PY - 2020 SN - 1792-1074 1792-1082 SP - 72 ST - YM155 sensitizes HeLa cells to TRAIL‑mediated apoptosis via cFLIP and survivin downregulation T2 - Oncology Letters TI - YM155 sensitizes HeLa cells to TRAIL‑mediated apoptosis via cFLIP and survivin downregulation UR - https://doi.org/10.3892/ol.2020.11933 VL - 20 ER -