X-ray irradiation altered chemosensitivity of a p53-null non-small cell lung cancer cell line
X-ray irradiation altered chemosensitivity of a p53-null non-small cell lung cancer cell line
复制标题
DOI：
10.1247/csf.31.47
复制
发表时间：
2006-01-01
影响因子：
1.5
通讯作者：
Nishioka, Takeshi
中科院分区：
文献类型：
--
作者：
Tsutsumi, Kaori;Yasuda, Motoaki;Nishioka, Takeshi
放射治疗是治疗多种癌症的有效方法。放射治疗技术的最新进展，例如调强放射治疗（IMRT）和三维（3D）放射治疗，可以将能量精确转移到肿瘤，从而提高了局部控制率。然而，放疗期间或放疗后耐受细胞的出现仍然存在问题。在本研究中，我们首先通过使用 6 MV X 射线进行 10 Gy 照射，从 H1299（p53 缺失的非小细胞肺癌细胞系）建立了细胞群。使用集落形成分析和 MTS 测定来确定该细胞群（称为 H1299-IR）的放射和化学敏感性。与亲本细胞系相比，H1299-IR的放射敏感性明显相同。 H1299 和 H1299-IR 均比 A549 细胞系具有更强的放射耐受性。然而，H1299-IR 对抗肿瘤药物顺铂变得更加敏感。暴露于25μg/ml顺铂2小时后，亲本细胞在MTS测定期间稳定生长，而H1299-IR细胞的敏感性在24小时和48小时时均加倍。对 30,000 多个 H1299-IR 基因（安捷伦技术）的微阵列分析显示，12 个和 15 个基因分别上调 (> 2.0) 和下调 (< 2.0)。 Rad51d（同源重组修复蛋白）基因下调2.8倍，而基质金属蛋白酶1（胶原酶-1）基因上调4.4倍。这些结果表明，当X射线放疗与随后或同时的顺铂化疗一起进行时，一些p53缺失的非小细胞肺癌可以成功治疗。
Radiotherapy is an effective approach to treating many types of cancer. Recent progress in radiotherapy technology, such as intensity-modulated radiation therapy (IMRT) and three-dimensional (3D) radiotherapy, allow precise energy transfer to the tumor, which has improved local control rates. However, the emergence of tolerant cells during or after radiotherapy remains problematic. In the present study, we first established a cell population from H1299, the p53-null non-small cell lung cancer cell line, by 10 Gy irradiation using 6 MV X-rays. The radio- and chemosensitivity of this cell population (referred to as H1299-IR) was determined using colony formation analyses and MTS assays. Compared with the parental cell line, the radiosensitivity of H1299-IR was apparently the same. H1299 and H1299-IR were both more radio tolerant than the A549 cell line. However, H1299-IR became significantly more sensitive to cisplatin, an antitumor agent. After exposure to 25 mu g/ml cisplatin for 2 h, parental cells steadily grew during the MTS assay, whereas the sensitivity of H1299-IR cells doubled both at 24 and 48 h. Microarray analysis of over 30,000 H1299-IR genes (Agilent Technology) revealed that 12 and 15 genes were up- (> 2.0) and down- (< 2.0) regulated, respectively. Rad51d (homologous recombination repair protein) gene was down-regulated 2.8-fold, whereas matrix metalloproteinase 1 (collagenase-1) gene was up-regulated 4.4-fold. These results indicated that some p53-null non-small cell lung cancers could be successfully treated when X-ray radiotherapy was administered with subsequent or concurrent cisplatin chemotherapy.