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布鲁司特醇或橘皮苷联合 5-氟尿嘧啶(5-FU)治疗结直肠癌细胞的潜在作用。

Potential cancer treatment effects of brusatol or eriodictyol combined with 5-fluorouracil (5-FU) in colorectal cancer cell.

机构信息

Faculty of Science, Department of Molecular Biology and Genetics, Muğla Sıtkı Koçman University, 48000, Mugla, Turkey.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2022 Sep;395(9):1109-1123. doi: 10.1007/s00210-022-02270-y. Epub 2022 Jul 20.

Abstract

Colorectal cancer is among the most frequently diagnosed cancers in patients today. In the treatment of this disease, combination or multicomponent therapy has been identified as a potential method to improve patient response and delay side effects. The aim of this study was to determine the effects on cell viability of commercial Bru and Erio used together with the anticancer drug 5-FU in the human colorectal cancer (CRC) cell line (HT-29 cell line) for the first time, as far as can be determined from available literature at this time. Additionally, the research seeks to study any potential effects on apoptosis. For this purpose, the effects of independent and combined treatments of the aforementioned agents on cell viability were investigated through the MTT experiment. Apoptotic effects were determined by Annexin V/PI and real-time PCR methods. In addition, a cell cycle analysis was used to determine the distribution of cells in the cycle. Data from experiments for 48 h showed that Bru, alone or in combination with 5-FU, is capable of causing an increase in the percentage of apoptotic cells in HT-29 cells compared to those of Erio alone or in combination with 5-FU. A significant increase in the level of bax and caspase-3 apoptotic genes was also detected in combinations of IC concentrations of Bru and 5-FU. These findings suggest that unlike Erio, Bru alone or in combination with 5-FU may be useful for increasing the effects of 5-FU used in the treatment of CRC and to provide data on alternative treatment approaches.

摘要

结直肠癌是当今患者中最常见的癌症之一。在这种疾病的治疗中,联合或多成分治疗已被确定为提高患者反应和延迟副作用的一种潜在方法。本研究的目的是首次确定在人结直肠癌细胞系(HT-29 细胞系)中,与抗癌药物 5-FU 联合使用商业 Bru 和 Erio 对细胞活力的影响,就目前可从现有文献中确定而言。此外,该研究旨在研究任何潜在的凋亡作用。为此,通过 MTT 实验研究了上述药物的独立和联合处理对细胞活力的影响。通过 Annexin V/PI 和实时 PCR 方法确定凋亡作用。此外,还进行了细胞周期分析以确定细胞在周期中的分布。48 h 实验数据表明,与单独使用 Erio 或与 5-FU 联合使用相比,Bru 单独或与 5-FU 联合使用能够增加 HT-29 细胞中凋亡细胞的百分比。还检测到 Bru 和 5-FU 的 IC 浓度组合中 bax 和 caspase-3 凋亡基因的水平显著增加。这些发现表明,与 Erio 不同,Bru 单独或与 5-FU 联合使用可能有助于增加 5-FU 在 CRC 治疗中的效果,并提供替代治疗方法的数据。

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