Division of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Fukumuro, Miyagino, Sendai, Miyagi, Japan.
Department of Applied Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Sakuragaoka, Kagoshima, Japan.
Technol Cancer Res Treat. 2020 Jan-Dec;19:1533033820980077. doi: 10.1177/1533033820980077.
Radiation therapy is a highly cost-effective treatment for cancer, but the existence of radio-resistant cells remains the most critical obstacle in radiotherapy. We have been established clinically relevant radioresistant (CRR) cell lines by exposure to a stepwise increase of fractionated X-rays. We are trying to overcome the radio-resistance by analyzing the properties of these cells. In this study, we tried to evaluate the effects of hydrogen peroxide (HO) on the CRR cells because this can evaluate the efficacy of Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas (KORTUC) that treats HO before irradiation. We also established HO-resistant cells to compare the radiation and HO resistant phenotype.
We used human cancer cell lines derived from hepatoblastoma (HepG2), oral squamous cell carcinoma (SAS), and cervical cancer (HeLa). We established HepG2, SAS, and HeLa CRR cells and HepG2, SAS, and HeLa HO-resistant cells. To evaluate their sensitivity to radiation or HO, high-density survival assay, or WST assay was performed. CellROX was used to detect intracellular Reactive Oxygen Species (ROS).
CRR cells were resistant to HO-induced cell death but HO-resistant cells were not resistant to irradiation. This phenotype of CRR cells was irreversible. The intracellular ROS was increased in parental cells after HO treatment for 3 h, but in CRR cells, no significant increase was observed.
Fractionated X-ray exposure induces HO resistance in CRR cells. Therefore, it is necessary to carry out cancer therapy such as KORTUC with the presence of these resistant cells in mind, and as the next stage, it would be necessary to investigate the appearance rate of these cells immediately and take countermeasures.
放射疗法是治疗癌症的一种高性价比的治疗方法，但放射抵抗细胞的存在仍然是放射治疗中最关键的障碍。我们通过逐步增加分割 X 射线照射建立了临床上相关的放射抵抗（CRR）细胞系。我们试图通过分析这些细胞的特性来克服放射抵抗。在这项研究中，我们试图评估过氧化氢（HO）对 CRR 细胞的影响，因为这可以评估在照射前治疗 HO 的 Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas（KORTUC）的疗效。我们还建立了 HO 耐药细胞，以比较辐射和 HO 耐药表型。
我们使用源自肝母细胞瘤（HepG2）、口腔鳞状细胞癌（SAS）和宫颈癌（HeLa）的人癌细胞系。我们建立了 HepG2、SAS 和 HeLa CRR 细胞以及 HepG2、SAS 和 HeLa HO 耐药细胞。为了评估它们对辐射或 HO 的敏感性，进行了高密度存活测定或 WST 测定。使用 CellROX 检测细胞内活性氧物种（ROS）。
CRR 细胞对 HO 诱导的细胞死亡具有抗性，但 HO 耐药细胞对辐射不具有抗性。这种 CRR 细胞的表型是不可逆的。HO 处理 3 小时后，亲本细胞中的细胞内 ROS 增加，但在 CRR 细胞中未观察到明显增加。
分割 X 射线照射诱导 CRR 细胞对 HO 的耐药性。因此，在考虑到这些耐药细胞的存在的情况下，有必要进行 KORTUC 等癌症治疗，作为下一阶段，有必要立即调查这些细胞的出现率并采取对策。
