当前位置: X-MOL 学术Curr. Pharm. Biotechnol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Effect of salinomycin on expression pattern of genes associated with apoptosis in endometrial cancer cell line.
Current Pharmaceutical Biotechnology ( IF 2.8 ) Pub Date : 2020-09-30 , DOI: 10.2174/1389201021666200513074022
Kamil Kiełbasiński 1 , Wojciech Peszek 2 , Beniamin O Grabarek 3, 4 , Dariusz Boroń 2, 3, 4 , Magdalena Wierzbik-Strońska 5 , Marcin Oplawski 2
Affiliation  

Background: Salinomycin is part of a group of ionophore antibiotics characterized by an activity towards tumor cells. To this day, the mechanism through which salinomycin induces their apoptosis is not fully known yet. The goal of this study was to assess the expression pattern of genes and the proteins coded by them connected with the process of programmed cell death in an endometrial cancer cell Ishikawa culture exposed to salinomycin and compared to the control.

Materials and Methods: Analysis of the effect of salinomycin on Ishikawa endometrial cancer cells (ECACC 99040201) included a cytotoxicity MTT test (with a concentration range of 0.1-100 μM), assessment of the induction of apoptosis and necrosis by salinomycin at a concentration of 1 μM as well the assessment of the expression of the genes chosen in the microarray experiment (microarray HG-U 133A_2) and the proteins coded by them connected with apoptosis (RTqPCR, ELISA assay). The statistical significance level for all analyses carried out as part of this study was p<0.05.

Results: It was observed that salinomycin causes the death of about 50% of cells treated by it (50.74±0.80% of all cells) at a concentration of 1μM. The decrease in the number of living cells was determined directly after treatment of the cells with the drug (time 0). The average percent of late apoptotic cells was 1.65±0.24% and 0.57±0.01% for necrotic cells throughout the entire observation period.

Discussion: Microarray analysis indicated the following number of mRNA differentiating the culture depending on the time of incubation with the drug: H_12 vs C = 114 mRNA, H_8 vs C = 84 mRNA, H_48 vs. C = 27 mRNA, whereas 5 mRNAs were expressed differently at all times. During the whole incubation period of the cells with the drug, the following dependence of the expression profile of the analyzed transcripts was observed: Bax>p53>FASL>BIRC5>BCL2L.

Conclusion: The analysis carried out indicated that salinomycin, at a concentration of 1 μM, stopped the proliferation of 50% of endometrial cancer cells, mainly by inducing the apoptotic process of the cells. The molecular exponent of the induction of programmed cell death was an observed increase in the transcriptional activity of pro-apoptotic genes: Bax;p53;FASL and a decrease in the expression of anti-apoptotic genes: BCL2L2; BIRC5.



中文翻译:

沙利霉素对子宫内膜癌细胞株凋亡相关基因表达模式的影响。

背景:沙利霉素是一组以对肿瘤细胞具有活性为特征的离子载体抗生素的一部分。到目前为止,尚不知道沙利霉素诱导细胞凋亡的机制。这项研究的目的是评估在暴露于盐霉素的子宫内膜癌细胞石川培养物中,基因和由其编码的蛋白质的表达模式与程序性细胞死亡过程有关,并与对照进行比较。

材料和方法:分析沙利霉素对石川子宫内膜癌细胞的作用(ECACC 99040201)包括细胞毒性MTT试验(浓度范围为0.1-100μM),评估浓度为0.1-100μM的沙利霉素诱导的细胞凋亡和坏死。还要评估1μM的微阵列实验(微阵列HG-U 133A_2)中选择的基因及其编码的蛋白与细胞凋亡相关的表达(RTqPCR,ELISA分析)。作为本研究的一部分,所有分析的统计显着性水平为p <0.05。

结果:观察到,在浓度为1μM的情况下,沙利霉素可导致约50%的细胞死亡(占所有细胞的50.74±0.80%)。在用药物处理细胞后立即确定了活细胞数量的减少(时间0)。在整个观察期间,坏死细胞的晚期凋亡细胞的平均百分比为1.65±0.24%和0.57±0.01%。

讨论:微阵列分析表明,根据与药物孵育时间的不同,mRNA可以分化培养物的数量如下:H_12 vs C = 114 mRNA,H_8 vs C = 84 mRNA,H_48 vs C = 27 mRNA,而表达了5个mRNA在任何时候都不同。在细胞与药物的整个温育期间,观察到以下对转录物表达谱的依赖性:Bax> p53> FASL> BIRC5> BCL2L。

结论:进行的分析表明,浓度为1μM的沙利霉素可通过诱导细胞凋亡过程来阻止50%的子宫内膜癌细胞增殖。诱导程序性细胞死亡的分子指数是观察到促凋亡基因:Bax; p53; FASL的转录活性增加,而抗凋亡基因:BCL2L2; BCL2L2的表达减少。BIRC5。

更新日期:2020-10-30
down
wechat
bug