In vitro studies on the modification of low-dose hyper-radiosensitivity in prostate cancer cells by incubation with genistein and estradiol.
In vitro studies on the modification of low-dose hyper-radiosensitivity in prostate cancer cells by incubation with genistein and estradiol.
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通过与染料木黄酮和雌二醇孵育，在前列腺癌细胞中低剂量超Xiosistitive的修饰的体外研究。
DOI：
10.1186/1748-717x-3-19
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发表时间：
2008-07-14
影响因子：
3.6
通讯作者：
Christiansen, Hans
中科院分区：
文献类型：
--
作者：
Hermann, Robert Michael;Wolff, Hendrik Andreas;Jarry, Hubertus;Thelen, Paul;Gruendker, Carsten;Rave-Fraenk, Margret;Schmidberger, Heinz;Christiansen, Hans
由于大多数前列腺癌（PC）表达雌激素受体，我们评估了放射和雌激素刺激（雌激素和染料木素）联合对体外前列腺癌细胞放射敏感性的影响。检测PC细胞LNCaP（雄激素敏感）和PC-3（雄激素非依赖性）。免疫染色法分析雌激素受体（ER）的表达。照射前24 h和照射后24 h，用染料木素10 μM和雌二醇10 μM在无fcs培养基中培养细胞。评估克隆成活、细胞周期变化和p21的表达。LNCaP同时表达ER-α和ER-β， PC-3不表达。LNCaP和PC-3与染料木素孵育可显著降低克隆存活率。雌二醇孵育在低浓度（0.01 μM）表现出刺激作用，而较高浓度则不影响存活。染料木黄酮10 μM和雌二醇10 μM均可增加LNCaP的低剂量超放射敏感性（HRS），而激素孵育可消除PC-3的HRS。在LNCaP细胞中，激素刺激可抑制4 Gy辐照后p21的诱导。在PC-3细胞中，4 Gy辐照后G2/M细胞比例增加。我们发现雌二醇或染料木素在ER-α和ER-β阳性LNCaP细胞中孵育低剂量后HRS增加。这具有很高的临床意义，因为这种肿瘤模型反映了局部进展，雄激素依赖性PC。相比之下，在ER-α和ER-β阴性的PC-3细胞中，我们观察到低剂量激素刺激的HRS消失。两种被测试的化合物对生存的影响是独立于ER和p53的。由于染料木黄酮和雌二醇在两种细胞系中的作用是相似的，因此ER-和p53的表达似乎都没有在相关的信号传导中发挥作用。然而，这两种化合物针对的是相同的分子开关。为了确定潜在的分子机制，还需要进一步的研究。
As the majority of prostate cancers (PC) express estrogen receptors, we evaluated the combination of radiation and estrogenic stimulation (estrogen and genistein) on the radiosensitivity of PC cells in vitro. PC cells LNCaP (androgen-sensitive) and PC-3 (androgen-independent) were evaluated. Estrogen receptor (ER) expression was analyzed by means of immunostaining. Cells were incubated in FCS-free media with genistein 10 μM and estradiol 10 μM 24 h before irradiation and up to 24 h after irradiation. Clonogenic survival, cell cycle changes, and expression of p21 were assessed. LNCaP expressed both ER-α and ER-β, PC-3 did not. Incubation of LNCaP and PC-3 with genistein resulted in a significant reduction of clonogenic survival. Incubation with estradiol exhibited in low concentrations (0.01 μM) stimulatory effects, while higher concentrations did not influence survival. Both genistein 10 μM and estradiol 10 μM increased low-dose hyper-radiosensitivity [HRS] in LNCaP, while hormonal incubation abolished HRS in PC-3. In LNCaP cells hormonal stimulation inhibited p21 induction after irradiation with 4 Gy. In PC-3 cells, the proportion of cells in G2/M was increased after irradiation with 4 Gy. We found an increased HRS to low irradiation doses after incubation with estradiol or genistein in ER-α and ER-β positive LNCaP cells. This is of high clinical interest, as this tumor model reflects a locally advanced, androgen dependent PC. In contrast, in ER-α and ER-β negative PC-3 cells we observed an abolishing of the HRS to low irradiation doses by hormonal stimulation. The effects of both tested compounds on survival were ER and p53 independent. Since genistein and estradiol effects in both cell lines were comparable, neither ER- nor p53-expression seemed to play a role in the linked signalling. Nevertheless both compounds targeted the same molecular switch. To identify the underlying molecular mechanisms, further studies are needed.