Herpes simplex virus-thymidine kinase/ganciclovir suppressed the growth of lung adenocarcinoma cells accompanied by premature senescence.

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. 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.