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YM155 sensitizes HeLa cells to TRAIL-mediated apoptosis via cFLIP and survivin downregulation

Title
YM155 sensitizes HeLa cells to TRAIL-mediated apoptosis via cFLIP and survivin downregulation
Author
Ramakrishna Suresh
Keywords
tumor necrosis factor‑related apoptosis inducing ligand therapy; YM155; HeLa cells; apoptosis; CASP8‑ and FADD‑like apoptosis regulator; death receptor 5; survivin
Issue Date
2020-10
Publisher
SPANDIDOS PUBL LTD
Citation
ONCOLOGY LETTERS, v. 20, no. 4, article no. 72, page. 1-10
Abstract
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 gamma H2A 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.
URI
https://www.spandidos-publications.com/10.3892/ol.2020.11933https://repository.hanyang.ac.kr/handle/20.500.11754/172045
ISSN
1792-1074; 1792-1082
DOI
10.3892/ol.2020.11933
Appears in Collections:
GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S](의생명공학전문대학원) > BIOMEDICAL SCIENCE(의생명과학과) > Articles
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