Radiobiological evaluation and correlation with the local effect model (LEM) of carbon ion radiation therapy and temozolomide in glioblastoma cell lines
Radiobiological evaluation and correlation with the local effect model (LEM) of carbon ion radiation therapy and temozolomide in glioblastoma cell lines
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DOI：
10.1080/09553000802641151
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发表时间：
2009-01-01
影响因子：
2.6
通讯作者：
Weyrather, Wilma K.
中科院分区：
文献类型：
--
作者：
Combs, Stephanie E.;Bohl, Jessica;Weyrather, Wilma K.
目的：目的探讨高线性能量转移（LET）碳辐射联合替莫唑胺（TMZ）对胶质母细胞瘤细胞株的细胞毒作用。方法和材料：用10 M或20 M TMZ处理表达野生型p53的细胞系U87-MG和同时表达突变型和野生型p53的细胞系LN 229后，用单能碳离子束（LET 172 keV/m）或扩展布拉格峰（LET 103 keV/m）照射。通过克隆形成存活试验测定细胞毒性，并检查细胞生长以及细胞周期进展。结果：突变型p53细胞对X射线照射的敏感性高于野生型p53细胞，且突变型p53细胞的G2期阻滞较短。高LET碳离子在两种细胞系中显示出增加的生物学有效性，这与Scholz等人引入的局部效应模型（LEM）的预测计算一致。细胞系LN 229比仅表达野生型p53的U87 MG细胞系对TMZ处理更敏感。TMZ和辐射的组合在两种细胞系中显示出累加效应。结论：高LET碳离子照射对胶质母细胞瘤细胞系的作用明显优于光子照射。TMZ的额外治疗可能提供很大的机会，特别是对于几种肿瘤类型。
Purpose: To investigate the cytotoxic effect of high linear-energy transfer (LET) carbon irradiation on glioblastoma cells lines in combination with temozolomide (TMZ). Methods and materials: The cell lines U87-MG expressing wild-type p53 and LN229 expressing both mutant and wild-type p53 were irradiated with monoenergetic carbon ion beams (LET 172keV/m) or an extended Bragg peak (LET 103keV/m) after treatment with 10M or 20M TMZ. Cytotoxicity was measured by a clonogenic survival assay, and cell growth as well as cell cycle progression, were examined. Results: The p53 mutant was more sensitive to X-ray irradiation than the p53 wild type cell line, which was also expressed in a shorter G2 block. High LET carbon ions show an increased biological effectiveness in both cell lines, which is consistent with the predictive calculations by the Local Effect Model (LEM) introduced by Scholz et al. The cell line LN229 was more sensitive to TMZ treatment than the U87MG cell line expressing wild-type p53 only. The combination of TMZ and irradiation showed an additive effect in both cell lines. Conclusion: High LET carbon ion irradiation is significantly more effective for glioblastoma cell lines compared to photon irradiation. An additional treatment with TMZ may offer a great chance especially for several tumor types.