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水醇提取物诱导人乳头瘤病毒18型(HPV18)永生化宫颈癌细胞(HeLa细胞)凋亡并改变其基因表达

Hydroalcoholic Extract Induces Apoptosis and Alters and Gene Expression in Hela Cervical Cancer Cells.

作者信息

Rezai Mehdi, Saravani Ramin, Sargazi Saman, Moudi Mahdiyeh, Jafari Shahroudi Mahdieh, Saravani Roya

机构信息

Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.

Cellular and Molecular Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.

出版信息

Rep Biochem Mol Biol. 2019 Oct;8(3):318-325.

Abstract

BACKGROUND

Inappropriate activation of the proto-oncogene LIN28B and inactivation of the p53 tumor suppressor, have been shown to have a critical role in tumorigenesis. Previous research has shown therapeutic potential for the use of herbal plants as an alternative strategy for cancer treatment. C. Koch is a plant that has been traditionally used for its medicinal properties. The aim of this study was to investigate the cytotoxic and apoptosis-inducing effect of hydroalcoholic extract () on HeLa cervical cancer cells and its effect on and expression.

METHODS

The cytotoxic activity of was evaluated on HeLa cells using a trypan blue exclusion assay. The Annexin V/PI double staining assay was used to evaluate the apoptosis-inducing effect of the extract. The expression of and mRNA was measured using the real-time-PCR method.

RESULTS

Treatment with was shown to induce cytotoxicity in both time and concentration-dependent manners (P<0.05). The proposition of HeLa cells undergoing apoptosis increased with increasing concentrations of (P<0.05). The mRNA levels of p53 increased following 12, 24, and 48 hours of AWHE treatment whereas the mRNA levels of were significantly decreased after 4 to 12 hours of treatment (p<0.05).

CONCLUSION

Our findings confirmed the pro-apoptotic function of on the cervical cancer HeLa cell line. This indicates that targeting the LIN28B signaling cascade may be a promising therapeutic strategy for cervical cancer. Further research is required to understand the therapeutic effects of in primary human cervical cancer cells and a pre-clinical cervical cancer model.

摘要

背景

原癌基因LIN28B的不适当激活和p53肿瘤抑制因子的失活在肿瘤发生中已显示出关键作用。先前的研究表明,使用草药植物作为癌症治疗的替代策略具有治疗潜力。C. Koch是一种传统上因其药用特性而被使用的植物。本研究的目的是研究水醇提取物()对HeLa宫颈癌细胞的细胞毒性和诱导凋亡作用及其对和表达的影响。

方法

使用台盼蓝排斥试验评估对HeLa细胞的细胞毒性活性。采用Annexin V/PI双染色试验评估提取物的诱导凋亡作用。使用实时PCR方法测量和mRNA的表达。

结果

处理显示出以时间和浓度依赖性方式诱导细胞毒性(P<0.05)。随着浓度的增加,发生凋亡的HeLa细胞比例增加(P<0.05)。AWHE处理12、2小时和48小时后,p53的mRNA水平升高,而处理4至12小时后,的mRNA水平显著降低(p<0.05)。

结论

我们的研究结果证实了对宫颈癌HeLa细胞系的促凋亡功能。这表明靶向LIN28B信号级联可能是一种有前景的宫颈癌治疗策略。需要进一步研究以了解在原代人宫颈癌细胞和临床前宫颈癌模型中的治疗效果。

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