| Du Mengjie,Yu Zuxiang,Adili Maheliya,et al.Radiosensitization effects of reactive oxygen species modulator 1 on human cutaneous melanoma cells[J].Chinese Journal of Radiological Medicine and Protection,2026,46(8):731-739 |
| Radiosensitization effects of reactive oxygen species modulator 1 on human cutaneous melanoma cells |
| Received:October 03, 2025 |
| DOI：10.3760/cma.j.cn112271-20251003-00353 |
| KeyWords:Melanoma|Reactive oxygen species modulator 1|Radiosensitivity|Apoptosis|Reactive oxygen species |
| FundProject:国家自然科学基金(82473574,82404200,U25A20151);四川省自然科学基金青年科学基金(25QNJJ4600) |
| Author Name | Affiliation | E-mail | | Du Mengjie | West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China | | | Yu Zuxiang | West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China | | | Adili Maheliya | West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China | | | Yang Tingyi | West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China | | | Wang Jiajia | School of Medicine, Xizang University, Lhasa 850000, China | | | Yu Daojiang | Department of Burns and Plastic Surgery, Nuclear Industry 416 Hospital, Chengdu 610051, China | | | Xiong Hai | School of Medicine, Xizang University, Lhasa 850000, China | | | Bai Hao | West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China | | | Zhang Shuyu | West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China | zhang.shuyu@hotmail.com |
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| Abstract:: |
| Objective To investigate the effects of reactive oxygen species modulator 1 (ROMO1) on the radiosensitivity of melanoma cells and to preliminarily explore the mechanisms underlying the effects, in order to provide experimental evidence for the research and development of radiosensitizers for melanoma treatment. Methods Human cutaneous melanoma cells A375 were investigated in this study. Based on irradiation and adenovirus treatment method, the cells were divided into four groups, namely the adenovirus negative control group (Ad-NC), the ROMO1 overexpression group (Ad-ROMO1), the adenovirus negative + irradiation group (Ad-NC + IR), and the ROMO1 overexpression + irradiation group (Ad-ROMO1 + IR), with 10 Gy X-ray irradiation adopted. Using the cell counting Kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) release assay, plate colony formation assay, wound healing assay, and flow cytometry, the effects of ROMO1 overexpression on the survival, proliferation, migration, apoptosis, reactive oxygen species (ROS) generation, and the mitochondrial membrane potential of the A375 cells were assessed. The expression levels of cell death related proteins were detected using Western blot analysis. Furthermore, differentially expressed genes (DEGs) were selected using the RNA sequencing (RNA-seq) method, followed by pathway enrichment analysis. Results Compared with the Ad-N + IR group, the Ad-ROMO1 + IR group exhibited suppressed viability of the A375 cells (t = 7.62, 7.25, P < 0.05), increased LDH release (t = 4.92, 3.77, P < 0.05), inhibited colony formation (t = 2.77, 8.07, 9.90, P < 0.05), and decreased cell migration (t = 8.19, P<0.05), as well as promoted apoptosis (t = 4.32, 26.01, P < 0.05), elevated ROS levels (t = 25.12, P < 0.05), and decreased mitochondrial membrane potential (t = 13.77, 8.98, P < 0.05). These results demonstrated distinct radiosensitization effects of ROMO1 overexpression. Western blot analysis indicated that after 10 Gy X-ray irradiation, the Ad-ROMO1 group showed upregulated expression of cleaved-caspase 3 and cleaved-PARP and an increased BAX/Bcl-2 ratio compared to the Ad-NC group. The analysis results derived using the RNA-seq method indicated that after irradiation, the Ad-ROMO1 group exhibited a total of 97 DEGs (58 upregulated and 39 downregulated genes) compared to the Ad-NC group. KEGG pathway enrichment analysis indicated that the upregulated DEGs were mainly enriched in signaling pathways involved in neuroactive ligand signaling, systemic lupus erythematosus (SLE), apoptosis, and cell cycle, as well as the JAK-STAT/Wnt signaling pathway. In contrast, the downregulated DEGs were primarily enriched in adenovirus infection-related pathways.Conclusions ROMO1 overexpression can enhance the radiosensitivity of human melanoma cells, potentially functioning by regulating ROS generation, promoting apoptosis, and modulating immune and inflammation-related signaling pathways. |
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