ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, India.
Anticancer Res. 2011 Nov;31(11):3851-7.
Adenoviral mediated suicide gene therapy has been shown to have a tumoricidal effect against a variety of tumor models. Although the efficacy of this treatment regimen has been verified, the molecular mechanism of Herpes simplex virus thymidine kinase gene (HSVtk)- and ganciclovir (GCV)-induced cell death is still not well established.
The mode of cell death by adenoviral (Adv)-HSVtk/GCV was examined in the head and neck squamous cell carcinoma cell line, NT8e.
The cell death was independent of apoptotic gene expression. Moreover apoptosis was not evident from cell cycle kinetic analysis. Adv-HSVtk/GCV treated cells showed time dependent accumulation of cells in the S-phase of the cell cycle although there was no increase in the "apoptotic peak" or sub-G1 population. Swelling of the cytoplasm without apparent nuclear condensation suggested a possible involvement of necrosis.
The apoptotic mechanism may not play a central role in the Adv-HSVtk/GCV induced NT8e cell death and other mechanisms should be considered.
腺病毒介导的自杀基因治疗已被证明对多种肿瘤模型具有杀伤作用。尽管这种治疗方案的疗效已得到验证，但单纯疱疹病毒胸苷激酶基因（HSVtk）和更昔洛韦（GCV）诱导细胞死亡的分子机制尚不完全清楚。
在头颈部鳞状细胞癌细胞系 NT8e 中，研究了腺病毒（Adv）-HSVtk/GCV 诱导的细胞死亡方式。
细胞死亡与凋亡基因表达无关。此外，细胞周期动力学分析也没有明显的凋亡迹象。Adv-HSVtk/GCV 处理的细胞尽管没有增加“凋亡峰”或 sub-G1 群体，但在 S 期细胞周期中表现出时间依赖性细胞积聚。细胞质肿胀而核无明显浓缩提示可能涉及坏死。
凋亡机制可能不是 Adv-HSVtk/GCV 诱导的 NT8e 细胞死亡的核心机制，应考虑其他机制。
