Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, Heidelberg, Germany.
Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany.
J Radiat Res. 2019 Oct 23;60(5):564-572. doi: 10.1093/jrr/rrz048.
To date, only few data exist on mechanisms underlying the human papillomavirus (HPV)-associated irradiation response. It has been suggested, that the viral E2 gene plays an important role in that context. The aim of the current study is to compare the effect of photon- and carbon-ion (12C)-radiation therapy (RT) on cells with different HPV and E2 gene status. We hypothesized that 12C-RT might overcome the radioresistance of E2 gene-disrupted cells. We analyzed four different cell lines that differed in HPV status or E2 gene status. Cells were irradiated with either photons or 12C. Clonogenic survival, cell cycle and expression of Rb and p53 were analyzed. Radiosensitivity seemed to be dependent on E2 gene status and type of RT. 12C-RT led to lower surviving fractions, indicating higher radiosensitivity even in cells with disrupted E2 gene. The observed relative biological effectiveness (RBE) of 12C-RT for C33a/Caski and W12/S12 was 1.3/4 and 2.7/2.5, respectively. Cell cycle regulation after both photon- and 12C-RT was dependent on HPV status and on E2 gene status. Furthermore, the effect of RT on expression of p53 and Rb seemed to be dependent on E2 gene status and type of RT. We showed that 12C-RT overcomes HPV-integration induced radioresistance. The effect of RT on cell cycle regulation as well as on expression of p53 and Rb seemed to be dependent on HPV status, E2 gene status and type of RT. Differences in Rb expression and cell cycle regulation may play a role for enhanced radiosensitivity to 12C-RT of cells with disrupted E2 gene.
迄今为止，关于人类乳头瘤病毒（HPV）相关辐射反应的机制仅有少量数据。有研究表明，病毒 E2 基因在这种情况下起着重要作用。本研究旨在比较不同 HPV 和 E2 基因状态的细胞对光子和碳离子（12C）放疗（RT）的反应。我们假设 12C-RT 可能克服 E2 基因缺失细胞的放射抵抗性。我们分析了 HPV 状态或 E2 基因状态不同的四种不同细胞系。细胞分别用光子或 12C 照射。克隆存活、细胞周期和 Rb 和 p53 的表达进行分析。放射敏感性似乎依赖于 E2 基因状态和 RT 类型。12C-RT 导致更低的存活分数，表明即使在 E2 基因缺失的细胞中也具有更高的放射敏感性。观察到的 12C-RT 对 C33a/Caski 和 W12/S12 的相对生物学效应（RBE）分别为 1.3/4 和 2.7/2.5。光子和 12C-RT 后细胞周期调控均依赖于 HPV 状态和 E2 基因状态。此外，RT 对 p53 和 Rb 表达的影响似乎依赖于 E2 基因状态和 RT 类型。我们表明 12C-RT 克服了 HPV 整合诱导的放射抵抗性。RT 对细胞周期调控以及 p53 和 Rb 表达的影响似乎取决于 HPV 状态、E2 基因状态和 RT 类型。Rb 表达和细胞周期调控的差异可能对 E2 基因缺失细胞对 12C-RT 的放射敏感性增强起作用。
