期刊
CANCER GENOMICS & PROTEOMICS
卷 18, 期 4, 页码 569-577出版社
INT INST ANTICANCER RESEARCH
DOI: 10.21873/cgp.20281
关键词
Mesenchymal stem cells; tumor necrosis factor-related apoptosis-inducing ligand; interferon-beta; genetic engineering
资金
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI17C1365]
- Basic Science Research Program through the National Research Foundation of Korea (NRF)
- Ministry of Education, Republic of Korea [NRF-2017R1D1A1A02019212]
The study found that TRAIL-overexpressing ASCs can be used to treat tumors, with ASC-IFN-beta secreting a higher level of TRAIL and showing enhanced therapeutic effects on H460 tumors.
Background/Aim: Mesenchymal stem cell-based tumor therapy is still limited due to the insufficient secretion of effectors and discrepancies between their in vitro and in vivo efficacy. We investigated whether genetically engineered adipose tissue-derived mesenchymal stem cells (ASCs) overexpressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) had inhibitory effects on H460 tumor growth both in vitro and in an H460 xenograft model. Materials and Methods: Genetically engineered adipose tissue-derived mesenchymal stem cells (ASCs) overexpressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were obtained from plasmid transfection with pCMV3-TRAIL and -interferon (IFN)-beta (producing ASC-TRAIL and ASC-IFN-beta, respectively). Death of H460 cells co-cultured with ASCs, ASC-TRAIL, and ASC-IFN-beta or exposed to their conditioned medium was evaluated via apoptosis and cytotoxicity assays. In addition, in an H460 xenograft model (n=10 per group), the antitumor potential of TRAIL-overexpressing, and IFN-beta-overexpressing ASCs was investigated. Results: Conditioned medium obtained from ASC-IFN-beta increased apoptosis of H460 cells more than did ASC-TRAIL. Additionally, in H460 xenograft models, while native ASCs promoted tumor growth, ASC-TRAIL and ASC-IFN-beta both dramatically suppressed tumor growth. Interestingly, in the context of ASC-IFN-beta, tumors were detected only in 20% of nude mice, with smaller sizes and lower weights than those of the control group. Conclusion: TRAIL-overexpressing ASCs can be used to treat tumors; ASC-IFN-beta in particular secrete a higher level of TRAIL.
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