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氟比洛芬对HeLa和HepG2细胞系的细胞毒性、遗传毒性和凋亡潜力评估。

Assessment of the cytotoxic, genotoxic, and apoptotic potential of flurbiprofen in HeLa and HepG2 cell lines.

作者信息

Bakır Elçin, Çal Tuğbagül, Aydın Dilsiz Sevtap, Canpınar Hande, Eken Ayşe, Ündeğer Bucurgat Ülkü

机构信息

Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey.

Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.

出版信息

J Biochem Mol Toxicol. 2021 Jun;35(6):1-11. doi: 10.1002/jbt.22770. Epub 2021 Mar 11.

Abstract

In the literature, the anticancer potential of flurbiprofen isn't fully understood. In this study, the cytotoxic, genotoxic, and apoptotic effects of flurbiprofen were evaluated in human cervical and liver cancer cells. Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and it was observed that cytotoxicity increased in a concentration- and time-dependent manner. Genotoxicity was determined using alkaline Comet assay. DNA damage increased in a concentration-dependent manner. Early apoptosis was evaluated using real-time polymerase chain reaction, and it was found that apoptotic gene levels increased while antiapoptotic gene levels decreased. Late apoptosis and cell cycle analyzes were determined using flow cytometry. No evidence of late apoptosis was observed, and no significant arrest was found in the cell cycle. In conclusion, it seems that flurbiprofen has a cytotoxic, genotoxic, and apoptotic effects in both human cancer cell lines. Moreover, the findings indicate that flurbiprofen is effective at the gene level and induces apoptosis with an intracellular pathway.

摘要

在文献中,氟比洛芬的抗癌潜力尚未完全明确。在本研究中,评估了氟比洛芬对人宫颈癌细胞和肝癌细胞的细胞毒性、遗传毒性及凋亡作用。通过3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐法测定细胞毒性,观察到细胞毒性呈浓度和时间依赖性增加。使用碱性彗星试验确定遗传毒性,DNA损伤呈浓度依赖性增加。通过实时聚合酶链反应评估早期凋亡,发现凋亡基因水平升高而抗凋亡基因水平降低。使用流式细胞术确定晚期凋亡和细胞周期分析。未观察到晚期凋亡的证据,且细胞周期未发现明显阻滞。总之,氟比洛芬似乎对两种人类癌细胞系均具有细胞毒性、遗传毒性和凋亡作用。此外,研究结果表明氟比洛芬在基因水平有效,并通过细胞内途径诱导凋亡。

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