Conditionally replicating adenovirus combined with gene-targeted radiotherapy induces apoptosis via TRAIL death receptors in MDA-MB-231 cells

Wu,Jia  Hui; Wang,Hong  Fang; Wang,Zhi   Cheng; Xu,Kai; Qi,Ya  Li; Li,Jin  Hua; Gong,Shou  Liang; Liu,Yang; Liu,Ya

doi:10.3892/mmr.2013.1488

Conditionally replicating adenovirus combined with gene-targeted radiotherapy induces apoptosis via TRAIL death receptors in MDA-MB-231 cells

Authors:
- Jia Hui Wu
- Hong Fang Wang
- Zhi Cheng Wang
- Kai Xu
- Ya Li Qi
- Jin Hua Li
- Shou Liang Gong
- Yang Liu
- Ya Liu
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Affiliations: Key Laboratory of Radiobiology, Ministry of Health, School of Public Health, Jilin University, Changchun, Jilin 130021, P.R. China, Beijing Center for Disease Control and Prevention, Beijing 100013, P.R. China, Department of Anesthesiology, Fifth Central Hospital of Tianjin, Tianjin 300450, P.R. China, Department of Nutrition and Food Hygiene, School of Pubic Health, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: May 23, 2013 https://doi.org/10.3892/mmr.2013.1488
Pages: 299-305

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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.

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