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7-香叶基氧杂蒽酮增强人前列腺癌细胞的放射敏感性。

7-Geranyloxcycoumarin enhances radio sensitivity in human prostate cancer cells.

机构信息

Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.

出版信息

Mol Biol Rep. 2023 Jul;50(7):5709-5717. doi: 10.1007/s11033-023-08439-9. Epub 2023 May 22.

Abstract

BACKGROUND

Prostate cancer is the second most prevalent and the fifth deadliest cancer among men worldwide. To improve radiotherapy outcome, we investigated the effects of 7-geranyloxycoumarin, also known as auraptene (AUR), on radiation response of prostate cancer cells.

METHODS AND RESULTS

PC3 cells were pretreated with 20 and 40 µM AUR for 24, 48 and 72 h, followed by X-ray exposure (2, 4 and 6 Gy). After 72 h recovery, cell viability was determined by alamar Blue assay. Flow cytometric analysis was performed to assess apoptosis induction, clonogenic assay was carried out to investigate clonogenic survival, and the expression of P53, BAX, BCL2, CCND1 and GATA6 was analyzed by quantitative polymerase chain reaction (qPCR). Cell viability assay indicated that toxic effects of radiation was enhanced by AUR, which was also confirmed by increased numbers of apoptotic cells and reduced amount of survival fraction. The qPCR results demonstrated significant induction of P53 and BAX, while the expression of BCL2, GATA6, and CCND1 was significantly downregulated.

CONCLUSION

The findings of the present study indicated, for the first time, that AUR improved radio sensitivity in prostate cancer cells, and thus, has the potential to be used in future clinical trials.

摘要

背景

前列腺癌是全球男性第二大常见癌症,也是第五大癌症死亡原因。为了提高放射治疗效果,我们研究了 7-香叶基香豆素(也称为auraptene,AUR)对前列腺癌细胞放射反应的影响。

方法和结果

PC3 细胞用 20 和 40 μM AUR 预处理 24、48 和 72 小时,然后进行 X 射线照射(2、4 和 6 Gy)。72 小时恢复后,通过 alamar Blue 测定法测定细胞活力。通过流式细胞术分析评估细胞凋亡诱导,通过集落形成实验进行集落存活分析,通过定量聚合酶链反应(qPCR)分析 P53、BAX、BCL2、CCND1 和 GATA6 的表达。细胞活力测定表明,AUR 增强了辐射的毒性作用,这也通过增加凋亡细胞数量和降低存活分数得到证实。qPCR 结果表明 P53 和 BAX 的表达显著诱导,而 BCL2、GATA6 和 CCND1 的表达则显著下调。

结论

本研究首次表明,AUR 提高了前列腺癌细胞的放射敏感性,因此具有在未来临床试验中应用的潜力。

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