{"title":"Herpes simplex virus-thymidine kinase/ganciclovir suppressed the growth of lung adenocarcinoma cells accompanied by premature senescence.","authors":"Nan-Xi Yu, Zhi-Hui Li, Qing-Hua Yu, Xue Lu, Ling Gao","doi":"10.21037/tcr-24-1815","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Extensive laboratory research and clinical trial results have shown that herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) system has a therapeutic effect on various tumours. This study focused on the role of HSV-TK/GCV system therapy for lung adenocarcinoma.</p><p><strong>Methods: </strong>Cell proliferation, migration, invasion, and premature senescence were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay, wound-healing assay, invasion assay, and β-galactosidase staining, respectively. Cells were transfected with adeno-associated virus (AAV) vector expressing HSV-TK (AAV-TK) or green fluorescent protein (GFP) (AAV-GFP, control). A murine xenograft model of Lewis cells was established to investigate the effect of HSV-TK/GCV system on tumour growth. Protein expression related to cell proliferation and senescence in tumour was analysed by immunohistochemical staining.</p><p><strong>Results: </strong>AAV-TK transfection combined with GCV treatment significantly inhibited the proliferation, migration and invasion of A549 and Lewis cells compared with AAV-GFP transfection. β-galactosidase activity assay indicated that the premature senescence of cells was enhanced after AAV-TK/GCV treatment. <i>In-vivo</i> tumour growth was significantly inhibited after intratumour injection of AAV-TK/GCV. Immunohistochemical staining showed that the expression of p16 protein significantly increased while proliferating cell nuclear antigen (PCNA) expression decreased in tumour tissue after AAV-TK administration, which conformed that the proliferation of tumour cells was inhibited by AAV-TK/GCV treatment.</p><p><strong>Conclusions: </strong>HSV-TK/GCV system could significantly inhibit the growth and metastasis of lung adenocarcinoma, accompanied by cell premature senescence.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"2797-2807"},"PeriodicalIF":1.7000,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170281/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-24-1815","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/14 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Extensive laboratory research and clinical trial results have shown that herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) system has a therapeutic effect on various tumours. This study focused on the role of HSV-TK/GCV system therapy for lung adenocarcinoma.
Methods: Cell proliferation, migration, invasion, and premature senescence were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay, wound-healing assay, invasion assay, and β-galactosidase staining, respectively. Cells were transfected with adeno-associated virus (AAV) vector expressing HSV-TK (AAV-TK) or green fluorescent protein (GFP) (AAV-GFP, control). A murine xenograft model of Lewis cells was established to investigate the effect of HSV-TK/GCV system on tumour growth. Protein expression related to cell proliferation and senescence in tumour was analysed by immunohistochemical staining.
Results: AAV-TK transfection combined with GCV treatment significantly inhibited the proliferation, migration and invasion of A549 and Lewis cells compared with AAV-GFP transfection. β-galactosidase activity assay indicated that the premature senescence of cells was enhanced after AAV-TK/GCV treatment. In-vivo tumour growth was significantly inhibited after intratumour injection of AAV-TK/GCV. Immunohistochemical staining showed that the expression of p16 protein significantly increased while proliferating cell nuclear antigen (PCNA) expression decreased in tumour tissue after AAV-TK administration, which conformed that the proliferation of tumour cells was inhibited by AAV-TK/GCV treatment.
Conclusions: HSV-TK/GCV system could significantly inhibit the growth and metastasis of lung adenocarcinoma, accompanied by cell premature senescence.
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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