氨磷汀在DNA损伤模型中不能保护甲状腺癌细胞。

Amifostine does not protect thyroid cancer cells in DNA damaging models.

作者信息

Klubo-Gwiezdzinska Joanna, Costello John, Jensen Kirk, Patel Aneeta, Tkavc Rok, Van Nostrand Douglas, Burman Kenneth D, Wartofsky Leonard, Vasko Vasyl

机构信息

National Institute of HealthNIDDK, Office 10 Center Drive, Bethesda, Maryland, USA.

Division of EndocrinologyDepartment of Medicine, Medstar Washington Hospital Center, Washington Hospital Center, Northwest, Washington, District of Columbia, USA.

出版信息

Endocr Connect. 2017 Oct;6(7):469-478. doi: 10.1530/EC-17-0138. Epub 2017 Aug 8.

DOI:10.1530/EC-17-0138

PMID:28790138

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5597971/

Abstract

BACKGROUND

Amifostine is a potent scavenger of reactive oxygen species that is used for the salivary gland protection during therapy with radioactive iodine for thyroid cancer. There are no data on the potential effect of amifostine on thyroid cancer cells.

METHODS

We investigated the effects of the active form of amifostine (WR-1065) on the response of thyroid cancer cells to treatment with DNA-damaging agents. WR-1065 was examined in human thyroid cancer cell lines (FTC133, TPC1, BCPAP and C643) and embryonic fibroblast cells NIH3T3. DNA damage was induced by exposure to HO (0.1 mM), by treatment with the radiomimetic neocarzinostatin (NCS 250 ng/mL) and by γ-radiation (6 Gy). DNA damage, cell viability and apoptosis were examined.

RESULTS

We demonstrated the selective action of WR-1065 (0.1 mM), which prevented oxidative stress-induced DNA damage in fibroblasts, but did not protect thyroid cancer cells from DNA damage and apoptosis documented by caspase-3 and PARP cleavage after exposure to HO, NCS and γ-radiation. Prolonged exposure to WR-1065 (0.1 mM for 24 h) was toxic for thyroid cancer cells; this treatment decreased the number of viable cells by 8% in C643 cells, 47% in TPC cells, 92% in BCPAP cells and 82% in FTC 133 cells. The cytotoxic effects of WR-1065 were not associated with induction of apoptosis.

CONCLUSIONS

Our data show that amifostine has no protective effect on thyroid cancer cells against DNA-damaging agents and suggest that amifostine will not attenuate the efficacy of radioiodine treatment in patients with thyroid cancer.

摘要

背景

氨磷汀是一种有效的活性氧清除剂，用于甲状腺癌放射性碘治疗期间的唾液腺保护。目前尚无关于氨磷汀对甲状腺癌细胞潜在影响的数据。

方法

我们研究了氨磷汀的活性形式（WR-1065）对甲状腺癌细胞对DNA损伤剂治疗反应的影响。在人甲状腺癌细胞系（FTC133、TPC1、BCPAP和C643）和胚胎成纤维细胞NIH3T3中检测WR-1065。通过暴露于HO（0.1 mM）、用放射模拟物新制癌菌素（NCS 250 ng/mL）处理以及γ射线照射（6 Gy）诱导DNA损伤。检测DNA损伤、细胞活力和凋亡情况。

结果

我们证明了WR-1065（0.1 mM）的选择性作用，它可预防成纤维细胞中氧化应激诱导的DNA损伤，但不能保护甲状腺癌细胞免受DNA损伤以及在暴露于HO、NCS和γ射线后由半胱天冬酶-3和PARP裂解所记录的凋亡。长时间暴露于WR-1065（0.1 mM，持续24小时）对甲状腺癌细胞有毒性；这种处理使C643细胞中的活细胞数量减少8%，TPC细胞中减少47%，BCPAP细胞中减少92%，FTC 133细胞中减少82%。WR-1065的细胞毒性作用与凋亡诱导无关。