Akino Yuichi, Teshima Teruki, Kihara Ayaka, Kodera-Suzumoto Yuko, Inaoka Miho, Higashiyama Shigeki, Furusawa Yoshiya, Matsuura Nariaki
Department of Radiation Oncology, Osaka University Graduate School of Medicine and Health Science, Suita, Osaka, Japan.
Int J Radiat Oncol Biol Phys. 2009 Oct 1;75(2):475-81. doi: 10.1016/j.ijrobp.2008.12.090.
Control of cancer metastasis is one of the most important issues in cancer treatment. We previously demonstrated that carbon particle irradiation suppresses the metastatic potential of cancer cells, and many studies have reported that photon irradiation promotes it. The purpose of this study was to investigate the effect of carbon beam on non-small-cell lung cancer (NSCLC) cell aggressiveness and gene expression.
A549 (lung adenocarcinoma) and EBC-1 (lung squamous cell carcinoma) cells were treated with 290 MeV/nucleon carbon ion beam at the Heavy Ion Medical Accelerator in Chiba or with 4-MV X-ray at Osaka University. We tested proliferative, migratory, and invasive activities by cell proliferation assay, Boyden chamber assay, and Matrigel chemoinvasion assay, respectively. cDNA microarray and reverse transcription polymerase chain reaction were also performed to assess mRNA expression alteration.
X-irradiation increased cell proliferation of A549 cells at 0.5 Gy, whereas high-dose X-ray reduced migration and invasion of A549 cells. By contrast, carbon beam irradiation did not enhance proliferation, and it reduced the migration and invasion capabilities of both A549 and EBC-1 cells more effectively than did X-irradiation. Carbon beam irradiation induced alteration of various gene expression profiles differently from X-ray irradiation. mRNA expression of ANLN, a homologue of anillin, was suppressed to 60% levels of basal expression in carbon beam-irradiated A549 cells after 12 h.
Carbon beam effectively suppresses the metastatic potential of A549 and EBC-1 cells. Carbon beam also has different effects on gene expressions, and downregulation of ANLN was induced only by carbon beam irradiation.
控制癌症转移是癌症治疗中最重要的问题之一。我们之前证明碳粒子辐射可抑制癌细胞的转移潜能，且许多研究报道光子辐射会促进癌细胞转移。本研究的目的是调查碳离子束对非小细胞肺癌（NSCLC）细胞侵袭性和基因表达的影响。
A549（肺腺癌）和EBC-1（肺鳞癌）细胞在千叶重离子医学加速器接受290 MeV/核子的碳离子束处理，或在大阪大学接受4-MV X射线处理。我们分别通过细胞增殖试验、博伊登小室试验和基质胶化学侵袭试验检测增殖、迁移和侵袭活性。还进行了cDNA微阵列和逆转录聚合酶链反应以评估mRNA表达变化。
0.5 Gy的X射线辐射增加了A549细胞的增殖，而高剂量X射线降低了A549细胞的迁移和侵袭能力。相比之下，碳离子束辐射并未增强增殖，且比X射线辐射更有效地降低了A549和EBC-1细胞的迁移和侵袭能力。碳离子束辐射诱导的各种基因表达谱变化与X射线辐射不同。在碳离子束辐射的A549细胞中，12小时后锚蛋白同源物ANLN的mRNA表达被抑制至基础表达水平的60%。
碳离子束可有效抑制A549和EBC-1细胞的转移潜能。碳离子束对基因表达也有不同影响，且仅碳离子束辐射可诱导ANLN下调。
