Abstract

Purpose

High LET including alpha radiation-based approaches have been proved as a promising mode for cancer therapy owing to their biophysical and radiobiological advantages compared to photon beams. Studies pertaining to effect of α-radiation on cancer cells are limited to cytotoxic high doses.

Materials and methods

In this study, human lung adenocarcinoma (A549) cells were α-irradiated using ²⁴¹Am α-irradiator and effects of low dose of alpha radiation on these cells was studied under in vitro and in vivo conditions.

Results

Clonogenic and other assays showed increased cellular proliferation at lower doses (1.36 and 6.8 cGy) but killing at higher doses (13.6–54.4 cGy). Further studies at low dose of alpha (1.36 cGy) showed increased TGF-β1 in the conditioned medium (CM) at early time point (24 h) but CM replacement did not affect the clonogenic survival. In these cells, increased phosphorylation of connexin 43 was correlated with decrease in gap-junction communication observed by dye transfer co-culture experiment. A decrease in caveolin-1 but increase in survivin expression was observed in low dose α-irradiated cells. An increase in cyclinD1 and decrease in Bcl-2, the target proteins of survivin, was observed in these cells. Low dose α-irradiated cancer cells transplanted in SCID mice showed significantly higher tumor volume, which was accompanied with an increased fraction of mitotic and PCNA/Ki67 positive cells in these tumor tissues.

Conclusions

Taken together, our results suggest an increase in proliferation and tumor volume at in vitro and in vivo levels, respectively, when A549 cells were irradiated with low dose of α-radiation. These findings may be relevant for a better understanding of radiobiological processes during high LET-based cancer radiotherapy.

中文翻译：

---

低剂量α辐射对人肺癌细胞的细胞增殖作用与连接蛋白43、caveolin-1和存活蛋白通路有关

摘要

目的

与光子束相比，包括基于 α 辐射的方法在内的高 LET 已被证明是一种有前途的癌症治疗模式，因为它们具有生物物理和放射生物学的优势。有关 α 辐射对癌细胞影响的研究仅限于细胞毒性高剂量。

材料和方法

在这项研究中，人肺腺癌 (A549) 细胞使用²⁴¹ Am α-辐照器进行α-辐照，并在体外和体内条件下研究了低剂量 α 辐射对这些细胞的影响。

结果

克隆形成和其他分析显示，在较低剂量（1.36 和 6.8 cGy）下细胞增殖增加，但在较高剂量（13.6-54.4 cGy）下会杀死细胞。低剂量 α (1.36 cGy) 的进一步研究表明，在早期时间点 (24 小时)，条件培养基 (CM) 中的 TGF-β1 增加，但 CM 替代不影响克隆存活。在这些细胞中，连接蛋白 43 磷酸化的增加与染料转移共培养实验观察到的间隙连接通讯的减少相关。在低剂量 α 辐照细胞中观察到caveolin-1 减少但survivin 表达增加。在这些细胞中观察到 cyclinD1 增加和 Bcl-2（存活蛋白的靶蛋白）减少。移植到 SCID 小鼠中的低剂量 α 辐射癌细胞显示出显着更高的肿瘤体积，

结论

总之，我们的结果表明，当 A549 细胞用低剂量的 α 辐射照射时，体外和体内水平的增殖和肿瘤体积分别增加。这些发现可能有助于更好地了解基于高 LET 的癌症放射治疗期间的放射生物学过程。