Role of p53 mutation in the effect of boron neutron capture therapy on oral squamous cell carcinoma.
Role of p53 mutation in the effect of boron neutron capture therapy on oral squamous cell carcinoma.
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DOI：
10.1186/1748-717x-4-63
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发表时间：
2009-12-11
期刊：
影响因子：
--
通讯作者：
Yura Y
中科院分区：
文献类型：
--
作者：
Fujita Y;Kato I;Iwai S;Ono K;Suzuki M;Sakurai Y;Ohnishi K;Ohnishi T;Yura Y
硼中子俘获疗法（BNCT）是一种选择性放射疗法，可有效治疗头颈部晚期恶性肿瘤以及脑肿瘤和皮肤黑色素瘤。为了阐明 p53 基因的作用，检查了 BNCT 对显示野生型 (SAS/neo) 或突变型 (SAS/mp53) p53 的口腔鳞状细胞癌 (SCC) 细胞的影响。在京都大学研究堆中，细胞在硼苯丙氨酸 (BPA) 存在下暴露于中子束。监测处理的细胞对集落形成、增殖、细胞周期和细胞周期相关蛋白表达的调节。当对 SAS/neo 和 SAS/mp53 细胞进行 BNCT 时，与 SAS/mp53 细胞相比，在 SAS/neo 中观察到对集落形成和细胞活力的更多抑制作用。在 SAS/neo 中观察到细胞周期在 G1 检查点停滞，但在 SAS/mp53 中未观察到。 SAS/neo 细胞中 BNCT 后 6 小时和 SAS/mp53 细胞中 48 小时后凋亡细胞增加。 p21 的表达仅在 SAS/neo 中被诱导，但 G2 停滞相关蛋白（包括 Wee1、cdc2 和 cyclin B1）在两种细胞系中均发生改变。这些结果表明，突变型口腔鳞状细胞癌比野生型p53的口腔鳞状细胞癌细胞对BNCT具有更强的抵抗力，并且缺乏G1阻滞和相关的细胞凋亡可能是这种抵抗的原因之一。在影响细胞周期的物理剂量下，BNCT 以 p53 依赖性和非依赖性方式抑制口腔 SCC 细胞。
Boron neutron capture therapy (BNCT) is a selective radiotherapy, being effective for the treatment of even advanced malignancies in head and neck regions as well as brain tumors and skin melanomas. To clarify the role of p53 gene, the effect of BNCT on oral squamous cell carcinoma (SCC) cells showing either wild- (SAS/neo) or mutant-type (SAS/mp53) p53 was examined. Cells were exposed to neutron beams in the presence of boronophenylalanine (BPA) at Kyoto University Research Reactor. Treated cells were monitored for modulations in colony formation, proliferation, cell cycle, and expression of cell cycle-associated proteins. When SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo compared with SAS/mp53 cells. Cell cycle arrest at the G1 checkpoint was observed in SAS/neo, but not in SAS/mp53. Apoptotic cells increased from 6 h after BNCT in SAS/neo and 48 h in SAS/mp53 cells. The expression of p21 was induced in SAS/neo only, but G2 arrest-associated proteins including Wee1, cdc2, and cyclin B1 were altered in both cell lines. These results indicate that oral SCC cells with mutant-type are more resistant to BNCT than those with wild-type p53, and that the lack of G1 arrest and related apoptosis may contribute to the resistance. At a physical dose affecting the cell cycle, BNCT inhibits oral SCC cells in p53-dependent and -independent manners.