title: Conditionally replicating adenovirus combined with gene-targeted radiotherapy induces apoptosis via TRAIL death receptors in MDA-MB-231 cells.
abstract: Malignant tumors are usually treated using monotherapies, which are not always effective. Therefore, combination therapies have gained increasing attention. The aims of this study were to investigate the effects of conditionally replicating adenovirus (CRAd) in combination with X-ray irradiation on the proliferation and apoptosis of MDA-MB-231 cells, as well as to determine the molecular mechanisms involved. MDA-MB-231 cells were treated simultaneously with CRAd and X-ray irradiation. Then, cell viability was measured using Cell Counting Kit-8. Cell apoptosis was assessed by flow cytometry with Annexin V and propidium iodide (PI) double-staining. The expression of tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), death receptor 5 (DR5), caspase-3 and caspase-8 mRNA was detected by quantitative polymerase chain reaction. The expression of TRAIL, DR5, caspase-3 and caspase-8 protein was measured by enzyme-linked immunosorbent assay (ELISA) and western blotting, respectively. The results showed that CRAd, in combination with irradiation, inhibited cell proliferation, promoted cell apoptosis and significantly increased the expression of TRAIL, DR5, caspase-3 and caspase-8 mRNA and proteins in MDA-MB-231 cells. Therefore, three aspects, including the targeted killing effect of CRAd, the apoptosis-promoting role of TRAIL and the direct killing effect of ionizing radiation to MDA-MB-231 cells, contribute to the mechanisms of CRAd in combination with irradiation to inhibit the proliferation of MDA-MB-231 cells. The pro-apoptotic effect may involve the interaction between TRAIL, DR5, caspase-3 and caspase-8.
authors.affiliation: Key Laboratory of Radiobiology, Ministry of Health, School of Public Health, Jilin University, Changchun, Jilin 130021, PR China.
authors.forename: Jia Hui
authors.initials: JH
authors.lastname: Wu
authors.forename: Hong Fang
authors.initials: HF
authors.lastname: Wang
authors.forename: Zhi Cheng
authors.initials: ZC
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.forename: Ya Li
authors.initials: YL
authors.lastname: Qi
authors.forename: Jin Hua
authors.initials: JH
authors.lastname: Li
authors.forename: Shou Liang
authors.initials: SL
authors.lastname: Gong
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics* / Q000528:radiation effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D051766:Early Growth Response Protein 1 / Q000235:genetics; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic; D011827:Radiation; D011878:Radiotherapy; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*
chemical_list: D051766:Early Growth Response Protein 1; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053148:Caspase 3; D053181:Caspase 8