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Cytoproliferative effect of low dose alpha radiation in human lung cancer cells is associated with connexin 43, caveolin-1, and survivin pathway
International Journal of Radiation Biology ( IF 2.6 ) Pub Date : 2021-01-08
Vasumathy Rajan, Badri Narain Pandey

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射线对人肺癌细胞的促细胞增生作用与连接蛋白43,caveolin-1和survivin途径相关

摘要

目的

包括基于alpha辐射的方法在内的高LET由于与光子束相比具有生物物理和放射生物学优势,因此已被证明是一种有前途的癌症治疗方法。关于α射线对癌细胞的作用的研究仅限于高剂量的细胞毒性。

材料和方法

在这项研究中,使用241 Amα辐射器对人肺腺癌(A549)细胞进行了α辐射,并在体外体内条件下研究了低剂量α辐射对这些细胞的影响。

结果

进行克隆试验和其他分析表明,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 h),条件培养基(CM)中的TGF-β1升高,但CM替代并不影响克隆形成存活。在这些细胞中,连接蛋白43的磷酸化增加与通过染料转移共培养实验观察到的间隙连接通讯减少有关。在低剂量α照射的细胞中,caveolin-1减少但survivin表达增加。在这些细胞中观察到cyclinD1的增加和survivin的靶蛋白Bcl-2的减少。在SCID小鼠中移植的低剂量经α照射的癌细胞显示出明显更高的肿瘤体积,

结论

两者合计,我们的结果表明,当用低剂量的α辐射照射A549细胞时,分别在体外体内水平上增殖和肿瘤体积增加。这些发现可能与更好地了解基于LET的高放疗过程中的放射生物学过程有关。

更新日期:2021-01-08
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