Mahmoudinasab Hamideh, Saadat Mostafa
Department of Biology, College of Sciences, Shiraz University , Shiraz, Iran .
DNA Cell Biol. 2018 Apr;37(4):330-335. doi: 10.1089/dna.2017.4108. Epub 2018 Feb 15.
Cisplatin [cis-dichlorodiammine platinum (II), CDDP], morphine (Mor), and electromagnetic field (EMF) induced oxidative stress. In this study, we tried to increase the cytotoxicity of CDDP in combination with Mor and/or EMF in MCF-7 and SH-SY5Y cells. Furthermore, we evaluate the expression levels of 11 antioxidant genes in both cell lines. We designed four treatments: CDDP alone, "CDDP+Mor," "CDDP+EMF," and "CDDP+Mor+EMF." Serial dilutions of CDDP, Mor (5.0 μM), and EMF (50 Hz, 0.50 mT, "15 min field-on/15 min field-off") were used for estimation of relative IC values. The mRNA expression levels of antioxidant genes were determined by real-time PCR. The IC value of CDDP in "CDDP+Mor+EMF" treatment was significantly higher than CDDP alone and "CDDP+Mor" treatments in both cell lines. Whereas the expression levels of antioxidant genes in the four treatments showed similar patterns in MCF-7 cells, in SH-SY5Y cells, most of the antioxidant genes showed an upregulation with "CDDP+EMF" and "CDDP+Mor+EMF" treatments. Moreover, significant differences in the number of upregulated genes were observed between different treatments in SH-SY5Y cells. The molecular mechanism of CDDP-reduced cytotoxicity in our designed combinations is probably different in MCF-7 and SH-SY5Y cells. CDDP in combination with EMF could protect SH-SY5Y cells from the cytotoxicity, whereas it has no significant change in MCF-7 cells.
顺铂[顺式二氯二氨合铂(II)，CDDP]、吗啡(Mor)和电磁场(EMF)可诱导氧化应激。在本研究中，我们试图增强CDDP与Mor和/或EMF联合使用时对MCF-7和SH-SY5Y细胞的细胞毒性。此外，我们评估了这两种细胞系中11种抗氧化基因的表达水平。我们设计了四种处理方式：单独使用CDDP、“CDDP+Mor”、“CDDP+EMF”和“CDDP+Mor+EMF”。使用CDDP、Mor(5.0 μM)和EMF(50 Hz，0.50 mT，“15分钟开/15分钟关”)的系列稀释液来估计相对IC值。通过实时PCR测定抗氧化基因的mRNA表达水平。在两种细胞系中，“CDDP+Mor+EMF”处理中CDDP的IC值显著高于单独使用CDDP和“CDDP+Mor”处理。在MCF-7细胞中，四种处理方式下抗氧化基因的表达水平呈现相似模式，而在SH-SY5Y细胞中，大多数抗氧化基因在“CDDP+EMF”和“CDDP+Mor+EMF”处理下呈上调。此外，在SH-SY5Y细胞的不同处理之间观察到上调基因数量的显著差异。在我们设计的组合中，CDDP降低细胞毒性的分子机制在MCF-7和SH-SY5Y细胞中可能不同。CDDP与EMF联合使用可保护SH-SY5Y细胞免受细胞毒性，而在MCF-7细胞中则无显著变化。
