Hasse Felix Christian, Koerber Stefan Alexander, Prigge Elena Sophie, Liermann Jakob, von Knebel Doeberitz Magnus, Debus Juergen, Sterzing Florian
Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
Department of Applied Tumor Biology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Clin Transl Radiat Oncol. 2019 Aug 20;19:52-58. doi: 10.1016/j.ctro.2019.08.003. eCollection 2019 Nov.
Radiosensitizers and heavy ion irradiation could improve therapy for female patients with malignant tumors located in the pelvic region through dose reduction. Aim of the study was to investigate the radiosensitizing potential of 2-deoxy-d-glucose (2-DG) in combination with carbon ion-irradiation (C) in representative cell lines of cancer in the female pelvic region.
The human cervix carcinoma cell line CaSki and the colorectal carcinoma cell line WiDr were used. 2-DG was employed in two different settings, pretreatment and treatment simultaneous to irradiation. Clonogenic survival, α and β values for application of the linear quadratic model and relative biological effectiveness (RBE) were determined. ANOVA tests were used for statistical group comparison. Isobolograms were generated for curve comparisons.
The comparison of monotherapy with C versus photons yielded RBE values of 2.4 for CaSki and 3.5 for WiDr along with a significant increase of α values in the C setting. 2-DG monotherapy reduced the colony formation of both cell lines. Radiosensitization was found in WiDr for the combination of photon irradiation with synchronous application of 2-DG. The same setup for C showed no radiosensitization, but rather an additive effect. In all settings with CaSki, the combination of irradiation and 2-DG exhibited additive properties.
The combination of 2-DG and photon therapy, as well as irradiation with carbon ions can overcome radioresistance of tumor cells such as WiDr.
放射增敏剂和重离子辐射可通过降低剂量来改善盆腔区域恶性肿瘤女性患者的治疗效果。本研究的目的是在女性盆腔区域癌症的代表性细胞系中，研究2-脱氧-D-葡萄糖（2-DG）与碳离子辐射（C）联合使用的放射增敏潜力。
使用人宫颈癌细胞系CaSki和结肠癌细胞系WiDr。2-DG在两种不同情况下使用，即预处理和与照射同时进行治疗。测定克隆形成存活率、线性二次模型应用的α和β值以及相对生物效应（RBE）。采用方差分析进行统计学组间比较。生成等效线图进行曲线比较。
C与光子单药治疗的比较显示，CaSki的RBE值为2.4，WiDr的RBE值为3.5，同时在C组中α值显著增加。2-DG单药治疗降低了两种细胞系的集落形成。在WiDr中发现光子照射与同步应用2-DG的联合具有放射增敏作用。C的相同设置未显示放射增敏作用，而是具有相加作用。在所有CaSki的设置中，照射与2-DG的联合表现出相加特性。
2-DG与光子治疗以及碳离子照射的联合可克服肿瘤细胞如WiDr的放射抗性。
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