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曲克芦丁对 HeLa 细胞系的抗癌和细胞毒性作用:宫颈癌的体外模型。

Anticancer and cytotoxic effects of troxerutin on HeLa cell line: an in-vitro model of cervical cancer.

机构信息

Physiology-Pharmacology Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.

Department of Physiology and Pharmacology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Khalije Fars Blvd., Pistachio Co. Street, Rafsanjan, P.O. Box: 77175-835, 7719617996, Iran.

出版信息

Mol Biol Rep. 2020 Aug;47(8):6135-6142. doi: 10.1007/s11033-020-05694-y. Epub 2020 Aug 1.

DOI:10.1007/s11033-020-05694-y
PMID:32740797
Abstract

Cervical cancer is one of the grave uterine tumors which leads to death in women worldwide. Troxerutin (TRX) as a bioflavonoid compound has many pharmacological effects such as anti-neoplastic, radioprotective, and anti-cancer. The present study was designed to examine the cytotoxic effect of TRX on human HeLa tumor cells. Human HeLa cells were cultured and treated with different doses of TRX (20-640 mg/ml) to evaluate the effective half-maximal inhibitory concentration (IC) after 24 h. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test was used for cell proliferation assay. Also, the Bax, Bcl-2, cleaved caspase-3, and tumor necrosis factor-α (TNF-α) protein expression levels were detected with immunoblotting analysis. The malondialdehyde (MDA) concentration, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity levels were measured via their commercial kits. Data were analyzed using one-way ANOVA. The result showed that TRX at 320 mg/ml concentration (IC) has a growth inhibitory effect against HeLa cells at 24 h treatment (P ˂ 0.01). Moreover, it increased the MDA concentration and also decreased the GPx and SOD activity levels at 320 mg/ml concentration versus control (P < 0.001). Also, TRX significantly up-regulated the Bax, cleaved caspase-3 and TNF-α proteins expression levels (P  <  0.01) and down-regulated the Bcl-2 protein expression in HeLa tumor cells at 320 mg/ml concentration compared to control (P < 0.05). Our study showed that 24 h of treatment with TRX (320 mg/ml) has apoptotic and growth inhibitory effects against HeLa cells. It can induce inflammation (at least via up-regulating the TNF-α protein expression) and oxidative stress in human HeLa cells.

摘要

宫颈癌是一种严重的子宫肿瘤,导致全球女性死亡。曲克芦丁(TRX)作为一种生物类黄酮化合物,具有多种药理作用,如抗肿瘤、放射保护和抗癌作用。本研究旨在研究 TRX 对人 HeLa 肿瘤细胞的细胞毒性作用。将人 HeLa 细胞培养并分别用不同剂量的 TRX(20-640mg/ml)处理 24 小时,以评估有效半抑制浓度(IC)。噻唑蓝(MTT)比色法用于细胞增殖试验。同时,用免疫印迹分析检测 Bax、Bcl-2、cleaved caspase-3 和肿瘤坏死因子-α(TNF-α)蛋白的表达水平。通过其商业试剂盒测量丙二醛(MDA)浓度、谷胱甘肽过氧化物酶(GPx)和超氧化物歧化酶(SOD)的活性水平。数据采用单因素方差分析进行分析。结果表明,TRX 在 320mg/ml 浓度(IC)时对 HeLa 细胞在 24 小时处理时有生长抑制作用(P<0.01)。此外,与对照组相比,320mg/ml 浓度时 MDA 浓度增加,GPx 和 SOD 活性降低(P<0.001)。此外,TRX 还显著上调 Bax、cleaved caspase-3 和 TNF-α蛋白的表达水平(P<0.01),并下调 Bcl-2 蛋白的表达(P<0.05)。我们的研究表明,TRX(320mg/ml)处理 24 小时对 HeLa 细胞具有促凋亡和生长抑制作用。它可以诱导人 HeLa 细胞的炎症(至少通过上调 TNF-α蛋白的表达)和氧化应激。

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