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铁对顺铂耐药的上皮性卵巢癌细胞中钙相关基因表达水平的影响。

The effect of iron on the expression levels of calcium related gene in cisplatin resistant epithelial ovarian cancer cells.

作者信息

Kucukkaya Bahire, Erdag Demet, Akbas Fahri, Yalcintepe Leman

机构信息

Department of Biophysics, Faculty of Medicine, Istanbul Yeni Yuzyil University, 34010 Istanbul, Turkey.

Department of Computer programming, Vocational School, Biruni University, 34010 Istanbul, Turkey.

出版信息

Explor Target Antitumor Ther. 2021;2(4):309-322. doi: 10.37349/etat.2021.00048. Epub 2021 Aug 30.

Abstract

AIM

Anticancer drugs (chemotherapeutics) used in cancer treatment (chemotherapy) lead to drug resistance. This study was conducted to investigate the possible effect of iron on calcium homeostasis in epithelial ovarian cancer cells (MDAH-2774) and cisplatin-resistant cells of the same cell line (MDAH-2774/DDP).

METHODS

To develop MDAH-2774/DDP cells, MDAH-2774 (MDAH) cells were treated with cisplatin in dose increases of 5 μM between 0 μM and 70 μM. The effect of iron on the viability of MDAH and MDAH/DDP cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test at the end of 24 h incubation.

RESULTS

At increasing iron concentrations in MDAH and MDAH/DDP cells, the mRNA gene of fifteen genes [inositol 1,4,5-triphosphate receptor , ryanodine receptor , sarco/endoplasmic reticulum Ca ATPase , Na/Ca exchange , and plasma membrane Ca ATPase ] associated with Ca differences in expression were determined by quantitative reverse transcription-polymerase chain reaction. Changes in and gene expressions were observed in iron treatment of MDAH/DDP cells, while changes were detected in iron treatment of MDAH cells in and expressions.

CONCLUSIONS

This changes in the expression of calcium channels, pumps, and exchange proteins in the epithelial ovarian cancer cell line and in cisplatin-resistant epithelial ovarian cancer cells suggest that iron may have an important role in regulating calcium homeostasis. Due to differences in the expression of genes that play of an important role in the regulation of calcium homeostasis in the effect of iron, drug resistance can be prevented by introducing a new perspective on the use of inhibitors and activators of these genes and thus cytostatic treatment strategies.

摘要

目的

用于癌症治疗(化疗)的抗癌药物(化学治疗剂)会导致耐药性。本研究旨在探讨铁对上皮性卵巢癌细胞(MDAH - 2774)及同一细胞系的顺铂耐药细胞(MDAH - 2774/DDP)钙稳态的可能影响。

方法

为培养MDAH - 2774/DDP细胞,MDAH - 2774(MDAH)细胞用顺铂处理,顺铂剂量在0 μM至70 μM之间以5 μM的增幅递增。孵育24小时结束时,通过3 -(4,5 - 二甲基噻唑 - 2 - 基)- 2,5 - 二苯基四氮唑溴盐试验测定铁对MDAH和MDAH/DDP细胞活力的影响。

结果

在MDAH和MDAH/DDP细胞中,随着铁浓度增加,通过定量逆转录 - 聚合酶链反应测定了与钙差异表达相关的15个基因[肌醇1,4,5 - 三磷酸受体、兰尼碱受体、肌浆/内质网钙ATP酶、钠/钙交换体和质膜钙ATP酶]的mRNA基因。在铁处理MDAH/DDP细胞时观察到[具体基因]和[具体基因]基因表达的变化,而在铁处理MDAH细胞时,在[具体基因]和[具体基因]表达中检测到变化。

结论

上皮性卵巢癌细胞系和顺铂耐药的上皮性卵巢癌细胞中钙通道、泵和交换蛋白表达的这种变化表明,铁可能在调节钙稳态中起重要作用。由于铁作用下在钙稳态调节中起重要作用的基因表达存在差异,通过引入关于这些基因抑制剂和激活剂使用的新视角,从而为细胞抑制治疗策略,可以预防耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5546/9400721/e15ad2e1b161/etat-02-100248-g001.jpg

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