Overexpression of SENP1 reduces the stemness capacity of osteosarcoma stem cells and increases their sensitivity to HSVtk/GCV
| العنوان: | Overexpression of SENP1 reduces the stemness capacity of osteosarcoma stem cells and increases their sensitivity to HSVtk/GCV |
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| المؤلفون: | Guowen Wang, Dianying Zhang, Xiaofang Ma, Yanxia Li, Xiaozhi Liu, Xiyun Bian, Lili Li, Fengting Liu |
| المصدر: | International Journal of Oncology |
| بيانات النشر: | Spandidos Publications, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, cancer stem cells, Oncology, 0301 basic medicine, Cancer Research, Cell, Apoptosis, chemotherapeutic drugs, Transduction, Genetic, Simplexvirus, RNA, Small Interfering, small ubiquitin-like modifiers, Genes, Transgenic, Suicide, Articles, Middle Aged, Cell cycle, Combined Modality Therapy, Cysteine Endopeptidases, medicine.anatomical_structure, Neoplastic Stem Cells, herpes simplex virus 1 thymidine kinase, Osteosarcoma, Female, Stem cell, Corrigendum, Adult, musculoskeletal diseases, medicine.medical_specialty, Adolescent, SENP1, ganciclovir, Mice, Nude, Biology, Antiviral Agents, Thymidine Kinase, Viral Proteins, Young Adult, 03 medical and health sciences, Cancer stem cell, Cell Line, Tumor, osteosarcoma, Internal medicine, Precursor cell, medicine, Animals, Humans, Sensitivity (control systems), neoplasms, Oncogene, Genetic Therapy, medicine.disease, Xenograft Model Antitumor Assays, 030104 developmental biology, Cell culture, Cancer research |
| الوصف: | Osteosarcoma stem cells are able to escape treatment with conventional chemotherapeutic drugs, as the majority of them are in a quiescent state. Recent reports have suggested that small ubiquitin‑like modifiers (SUMOs) serve important roles in the maintenance of cancer stem cell stemness. Therefore, a potential strategy to increase the effectiveness of chemotherapeutic agents is to interfere with SUMO modification of proteins associated with the maintenance of stemness in osteosarcoma stem cells. The present study revealed a significant decrease in the expression of SUMO1 specific peptidase 1 (SENP1) in osteosarcoma tissues and osteosarcoma cell lines, and SENP1 expression was much lower in osteosarcoma stem cells than in non‑cancer stem cells. Further experiments indicated that the low levels of SENP1 were essential for maintenance of stemness in osteosarcoma stem cells. Overexpression of SENP1 resulted in a marked decrease in the maintenance of stemness, but only slightly induced apoptosis of osteosarcoma cells, which is crucial to reduce the side effects of drugs on normal precursor cells. Finally, SENP1 overexpression led to a significant increase in the sensitivity of osteosarcoma stem cells to the herpes simplex virus 1 thymidine kinase gene in combination with ganciclovir in vitro and in vivo. In conclusion, the present study described a novel method to increase the sensitivity of osteosarcoma stem cells to chemotherapeutic drugs. Notably, this approach may significantly reduce the required dose of conventional chemotherapeutic drugs and reduce side effects. |
| تدمد: | 1791-2423 1019-6439 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::abbf7730f45e4187ff9e848e01567e60Test https://doi.org/10.3892/ijo.2018.4537Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....abbf7730f45e4187ff9e848e01567e60 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17912423 10196439 |
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