The Effects of Hydrogen Peroxide and/or Radiation on the Survival of Clinically Relevant Radioresistant Cells.

The Effects of Hydrogen Peroxide and/or Radiation on the Survival of Clinically Relevant Radioresistant Cells.
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DOI:
10.1177/1533033820980077
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发表时间:
2020-01
影响因子:
2.8
通讯作者:
Sato T
Sato T
中科院分区:
医学4区
文献类型:
--
作者:
Kuwahara Y;Tomita K;Roudkenar MH;Roushandeh AM;Urushihara Y;Igarashi K;Nagasawa T;Kurimasa A;Fukumoto M;Sato T

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放射治疗是一种高性价比的癌症治疗方法,但放射抵抗细胞的存在仍然是放射治疗中最关键的障碍。我们已经建立了临床相关的放射抵抗(CRR)细胞系,通过逐步增加分割X射线的暴露。我们正试图通过分析这些细胞的特性来克服辐射抗性。在本研究中,我们试图评估过氧化氢(H_2O_2)对CRR细胞的影响,因为这可以评估Kochi Oxydol放射疗法(KORTUC)在照射前处理H_2O_2的疗效。我们还建立了抗H_2O_2的细胞来比较辐射和H_2O_2抗性的表型。我们使用来源于肝母细胞瘤(HepG2)、口腔鳞状细胞癌(SAS)和宫颈癌(HeLa)的人类癌细胞系。我们建立了HepG2、SAS和HeLa CRR细胞,以及对H_2O_2具有抗性的细胞。为评价其对辐射或过氧化氢的敏感性,进行了高密度存活试验或WST试验。用CellROXTM检测细胞内活性氧(ROS)。CRR细胞能抵抗H_2O_2诱导的细胞死亡,而H_2O_2抗性细胞不能抵抗辐射。CRR细胞的这种表型是不可逆的。H_2O_2处理亲本细胞3h后,细胞内ROS明显增加,而CRR细胞内ROS无明显增加。分步X射线照射可诱导CRR细胞对过氧化氢的抗性。因此,有必要在进行KORTUC等癌症治疗时考虑到这些耐药细胞的存在,下一阶段,有必要立即调查这些细胞的出现率并采取对策。
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 (H2O2) on the CRR cells because this can evaluate the efficacy of Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas (KORTUC) that treats H2O2 before irradiation. We also established H2O2-resistant cells to compare the radiation and H2O2 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 H2O2-resistant cells. To evaluate their sensitivity to radiation or H2O2, high-density survival assay, or WST assay was performed. CellROXTM was used to detect intracellular Reactive Oxygen Species (ROS). CRR cells were resistant to H2O2-induced cell death but H2O2-resistant cells were not resistant to irradiation. This phenotype of CRR cells was irreversible. The intracellular ROS was increased in parental cells after H2O2 treatment for 3 h, but in CRR cells, no significant increase was observed. Fractionated X-ray exposure induces H2O2 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.
表柔比星和环磷酰胺或紫杉烷诱导化疗后,IV 期原发性乳腺癌患者残余病灶对新型酶靶向放射增敏治疗 (KORTUC II) 的治疗反应。
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