Melatonin enhances radiofrequency-induced NK antitumor immunity, causing cancer metabolism reprogramming and inhibition of multiple pulmonary tumor development
| Autor: | Menghuan Zhang, Baigenzhin Abay, Yufeng Shi, Xiangyun Chen, Tiansheng Zheng, Shumeng Lin, Bingjie Hao, Xiao Xu, Russel J. Reiter, Yanbei Ren, Liduo Yue, Guojie Chen, Lihong Fan, Ming Li |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Cancer Research Lung Neoplasms Neoplasm Residual QH301-705.5 Radiofrequency ablation Kaplan-Meier Estimate Malignancy Article Malignant transformation law.invention Mice law Genetics Animals Humans Medicine Hedgehog Proteins Biology (General) Lung cancer Wnt Signaling Pathway Aged Cell Proliferation Melatonin Aged 80 and over Mitogen-Activated Protein Kinase Kinases Radiofrequency Ablation Tumor microenvironment Multiple Pulmonary Nodules Lung business.industry NF-kappa B Middle Aged medicine.disease Combined Modality Therapy Warburg effect Progression-Free Survival Killer Cells Natural Treatment Outcome medicine.anatomical_structure Cancer research Heterografts Female business |
| Zdroj: | Signal Transduction and Targeted Therapy Signal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-14 (2021) |
| ISSN: | 2059-3635 |
| DOI: | 10.1038/s41392-021-00745-7 |
| Popis: | Surgery is the common treatment for early lung cancer with multiple pulmonary nodules, but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic areas. In this study, we found that a combined treatment of local radiofrequency ablation (RFA) and melatonin (MLT) greatly improved clinical outcomes for early lung cancer patients with multiple pulmonary nodules by minimizing lung function injury and reducing the probability of malignant transformation or enlargement of nodules in non-ablated areas. Mechanically, as demonstrated in an associated mouse lung tumor model, RFA not only effectively remove treated tumors but also stimulate antitumor immunity, which could inhibit tumor growth in non-ablated areas. MLT enhanced RFA-stimulated NK activity and exerted synergistic antitumor effects with RFA. Transcriptomics and proteomics analyses of residual tumor tissues revealed enhanced oxidative phosphorylation and reduced acidification as well as hypoxia in the tumor microenvironment, which suggests reprogrammed tumor metabolism after combined treatment with RFA and MLT. Analysis of residual tumor further revealed the depressed activity of MAPK, NF-kappa B, Wnt, and Hedgehog pathways and upregulated P53 pathway in tumors, which was in line with the inhibited tumor growth. Combined RFA and MLT treatment also reversed the Warburg effect and decreased tumor malignancy. These findings thus demonstrated that combined treatment of RFA and MLT effectively inhibited the malignancy of non-ablated nodules and provided an innovative non-invasive strategy for treating early lung tumors with multiple pulmonary nodules. Trial registration: www.chictr.org.cn, identifier ChiCTR2100042695, http://www.chictr.org.cn/showproj.aspx?proj=120931. |
| Databáze: | OpenAIRE |
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