Yu Nan-Xi, Li Zhi-Hui, Yu Qing-Hua, Lu Xue, Gao Ling
China CDC Key Laboratory of Radiological Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing, China.
Department of Thoracic Surgery, Aviation General Hospital of China Medical University, Beijing, China.
Transl Cancer Res. 2025 May 30;14(5):2797-2807. doi: 10.21037/tcr-24-1815. Epub 2025 May 14.
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.
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.
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. 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.
HSV-TK/GCV system could significantly inhibit the growth and metastasis of lung adenocarcinoma, accompanied by cell premature senescence.
大量实验室研究和临床试验结果表明，单纯疱疹病毒胸苷激酶/更昔洛韦（HSV-TK/GCV）系统对多种肿瘤具有治疗作用。本研究聚焦于HSV-TK/GCV系统治疗肺腺癌的作用。
分别采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐（MTT）法、集落形成试验、伤口愈合试验、侵袭试验和β-半乳糖苷酶染色检测细胞增殖、迁移、侵袭和早衰情况。用表达HSV-TK的腺相关病毒（AAV）载体（AAV-TK）或绿色荧光蛋白（GFP）（AAV-GFP，对照）转染细胞。建立Lewis细胞小鼠异种移植模型，以研究HSV-TK/GCV系统对肿瘤生长的影响。通过免疫组织化学染色分析肿瘤中与细胞增殖和衰老相关的蛋白质表达。
与AAV-GFP转染相比，AAV-TK转染联合GCV处理显著抑制了A549和Lewis细胞的增殖、迁移和侵袭。β-半乳糖苷酶活性检测表明，AAV-TK/GCV处理后细胞早衰增强。瘤内注射AAV-TK/GCV后肿瘤生长显著受到抑制。免疫组织化学染色显示，给予AAV-TK后肿瘤组织中p16蛋白表达显著增加，而增殖细胞核抗原（PCNA）表达降低，这证实AAV-TK/GCV处理抑制了肿瘤细胞的增殖。
HSV-TK/GCV系统可显著抑制肺腺癌的生长和转移，并伴有细胞早衰。
