Evaluation of chemoradiotherapy with carbon ions and the influence of p53 mutational status in the colorectal carcinoma cell line HCT 116
Evaluation of chemoradiotherapy with carbon ions and the influence of p53 mutational status in the colorectal carcinoma cell line HCT 116
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DOI：
10.1700/1778.19278
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发表时间：
2014-11-01
期刊：
影响因子：
1.9
通讯作者：
Combs, Stephanie E.
中科院分区：
文献类型：
--
作者：
Adeberg, Sebastian;Baris, Daniela;Combs, Stephanie E.
目标和背景。重离子治疗在治疗复发性结直肠癌方面显示出有希望的结果。本研究评估了五种不同的细胞抑制剂联合碳 (C12) 离子和光子放射治疗对 p53 状态不同的两种同基因结直肠癌细胞系的影响。方法和研究设计。使用人结肠癌细胞系 HCT 116 wt 和同基因 p53 缺陷细胞系 HCT 116 p53 -/- 进行克隆形成存活分析。使用线性加速器施加高达 10 Gy 的单光子剂量（6 MV X 射线）。在海德堡离子束治疗中心进行了高达 3 Gy 的碳离子照射，水平光束线提供了扩展的布拉格峰，平均线性能量转移为 103 keV/μm。五种不同的细胞抑制剂与光子和碳离子放射疗法联合应用。结果。两种细胞系对光子和碳离子都表现出相似的反应，而用碳离子处理则产生了优异的相对生物效率。单独使用伊立替康和紫杉醇在治疗野生型细胞时表现出高毒性。 p53 -/- 细胞系的细胞死亡存在显着差异。在这里，紫杉醇和吉西他滨的单一治疗产生了良好的反应率。碳离子与吉西他滨、伊立替康或紫杉醇的组合显示出高反应率。用碳离子和替莫唑胺照射后，细胞存活率取决于p53状态，野生型细胞的存活率降低。结论。伊立替康和紫杉醇是治疗 HCT 116 wt 细胞的有效方法，而紫杉醇和吉西他滨可以成功治疗 p53 缺陷的 HCT 116 细胞。碳离子和化疗的联合治疗方式具有良好的疗效，可能为未来复发性结直肠癌提供新的治疗机会。
Aims and background. Heavy ion therapy has shown promising results in the treatment of recurrent colorectal carcinoma. The present study evaluates the effect of five different cytostatic agents in combination with radiotherapy with carbon (C12) ions and photons in two isogenic colorectal cancer cell lines differing in p53 status.Methods and study design. Clonogenic survival analyses were performed using the human colon cancer cell lines HCT 116 wt and the isogenic p53 deficient cell line HCT 116 p53 -/-. Single photon doses (6 MV X-rays) up to 10 Gy were applied using a linear accelerator. Carbon ion irradiation up to 3 Gy was performed at the Heidelberg Ion-Beam Therapy Center with the horizontal beamline delivering an extended Bragg peak with an average linear energy transfer of 103 keV/mu m. Five different cytostatic agents were applied in combinations with photon and carbon ion radiotherapy.Results. Both cell lines showed a similar response to photons and carbon ions, whereas treatment with carbon ions resulted in a superior relative biological efficiency. Irinotecan and paclitaxel alone showed high toxicity in the treatment of wildtype cells. A notable difference was observed on the cell death of p53 -/- cell lines. Here, single treatment with paclitaxel and gemcitabine resulted in good response rates. Combinations of carbon ions with gemcitabine, irinotecan or paclitaxel revealed high response rates. After irradiation with carbon ions and temozolomide, cell survival rates depended on p53 status, with a decreased survival rate in wildtype cells.Conclusions. Irinotecan and paclitaxel are an effective treatment for HCT 116 wt cells, whereas HCT 116 cells with p53 deficiency can be treated successfully with paclitaxel and gemcitabine. Combined treatment modalities with carbon ions and chemotherapy provide great effectiveness that may offer new treatment opportunities for recurrent colorectal cancer in the future.