Abstract

Purpose To examine whether hypoxia and Hif-1α affect sensitivity of murine squamous cell carcinoma cells to boron neutron capture therapy (BNCT).

Materials and methods SCC VII and SCC VII Hif-1α-deficient mouse tumor cells were incubated under normoxic or hypoxic conditions, and cell survival after BNCT was assessed. The intracellular concentration of the ¹⁰B-carrier, boronophenylalanine-¹⁰B (BPA), was estimated using an autoradiography technique. The expression profile of SLC7A5, which is involved in the uptake of BPA, and the amount of DNA damage caused by BNCT with BPA were examined. A cell survival assay was performed on cell suspensions prepared from tumor-bearing mice.

Results Hypoxia ameliorated SCC VII cell survival after neutron irradiation with BPA, but not BSH. Hypoxia-treated SCC VII cells showed decreased intracellular concentrations of BPA and the down-regulated expression of the SLC7A5 protein. BPA uptake and the SLC7A5 protein were not decreased in hypoxia-treated Hif-1α-deficient cells, the survival of which was lower than that of SCC VII cells. More DNA damage was induced in SCC VII Hif-1α-deficient cells than in SCC VII cells. In experiments using tumor-bearing mice, the survival of SCC VII Hif-1α-deficient cells was lower than that of SCC VII cells.

Conclusion. Hypoxia may decrease the effects of BNCT with BPA, whereas the disruption of Hif-1α enhanced sensitivity to BNCT with BPA.

摘要

目的探讨缺氧和Hif-1α是否影响鼠鳞状细胞癌细胞对硼中子俘获疗法（BNCT）的敏感性。

材料和方法SCC VII 和 SCC VII Hif-1α 缺陷小鼠肿瘤细胞在常氧或缺氧条件下孵育，并评估 BNCT 后的细胞存活率。使用放射自显影技术估计¹⁰ B-载体、硼苯丙氨酸- ¹⁰ B (BPA)的细胞内浓度。检查了参与 BPA 摄取的 SLC7A5 的表达谱，以及 BPA BNCT 引起的 DNA 损伤量。对从荷瘤小鼠制备的细胞悬液进行细胞存活测定。

结果在用 BPA 而非 BSH 进行中子照射后，缺氧改善了 SCC VII 细胞的存活率。缺氧处理的 SCC VII 细胞显示出细胞内 BPA 浓度降低和 SLC7A5 蛋白表达下调。在缺氧处理的 Hif-1α 缺陷细胞中，BPA 摄取和 SLC7A5 蛋白没有降低，其存活率低于 SCC VII 细胞。与 SCC VII 细胞相比，SCC VII Hif-1α 缺陷细胞中诱导的 DNA 损伤更多。在使用荷瘤小鼠的实验中，SCC VII Hif-1α 缺陷细胞的存活率低于 SCC VII 细胞的存活率。

结论。缺氧可能会降低 BNCT 对 BPA 的影响，而 Hif-1α 的破坏增强了对 BPA BNCT 的敏感性。