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探讨牛磺罗定在诱导结肠癌细胞迁移和脱落中的作用:一项初步的体外研究。

Exploring the potential of taurolidine in inducing mobilization and detachment of colon cancer cells: a preliminary in-vitro study.

机构信息

Department of Biochemistry and Molecular Biology, Wroclaw University of Environmental and Life Sciences, 50-375, Wroclaw, Wroclaw, Poland.

2nd Department of General Surgery and Surgical Oncology, Wroclaw Medical University, 50-556, Wroclaw, Wroclaw, Poland.

出版信息

BMC Pharmacol Toxicol. 2022 Jun 13;23(1):38. doi: 10.1186/s40360-022-00572-8.

Abstract

BACKGROUND

Recently, taurolidine has been intensively studied on a variety of in-vitro cancer cell-lines and first data exhibit encouraging antitumoral effects. While the clinical use of taurolidine is considered, some studies with in-vivo experiments contradict this beneficial effect and even indicate advanced cancer growth. The aim of this study is to further investigate this paradox in-vivo effect by taurolidine and closely analyze the interaction of cancer cells with the surrounding environment following taurolidine exposure.

METHODS

HT-29 (ATCC® HTB-38™) cells were treated with taurolidine at different concentrations and oxaliplatin using an in-vitro model. Morphological changes with respect to increasing taurolidine dosage were visualized and monitored using electron microscopy. Cytotoxicity of the agents as well as extent of cellular detachment by mechanical stress was measured for each substance using a colorimetric MTS assay.

RESULTS

Both taurolidine and oxaliplatin exhibit cell toxicity on colon cancer cells. Taurolidine reshapes colon cancer cells from round into spheric cells and further induces cluster formation. When exposed to mechanical stress, taurolidine significantly enhances detachment of adherent colon carcinoma cells compared to the control (p < 0.05) and the oxaliplatin group (p < 0.05). This effect is dose dependent.

CONCLUSIONS

Beside its cytotoxic effects, taurolidine could also change mechanical interactions of cancer cells with their environment. Local cancer cell conglomerates could be mechanically mobilized and may cause metastatic growth further downstream. The significance of changes in cellular morphology caused by taurolidine as well as its interaction with the microenvironment must be further addressed in clinical cancer therapies. Further clinical studies are needed to evaluate both the safety and efficacy of taurolidine for the treatment of peritoneal surface malignancies.

摘要

背景

最近,研究人员对牛磺罗定在各种体外癌细胞系上进行了深入研究,初步数据显示出令人鼓舞的抗肿瘤作用。虽然牛磺罗定的临床应用正在被考虑,但一些体内实验研究结果与这种有益的效果相矛盾,甚至表明癌症生长加速。本研究旨在通过牛磺罗定进一步研究这种矛盾的体内效应,并密切分析牛磺罗定暴露后癌细胞与周围环境的相互作用。

方法

采用体外模型,用不同浓度的牛磺罗定和奥沙利铂处理 HT-29(ATCC® HTB-38™)细胞。用电子显微镜观察并监测随着牛磺罗定剂量增加而出现的形态变化。用比色 MTS 测定法测定每种物质的细胞毒性以及机械应激引起的细胞脱落程度。

结果

牛磺罗定和奥沙利铂均对结肠癌细胞具有细胞毒性。牛磺罗定将结肠癌细胞从圆形重塑为球形,并进一步诱导细胞簇形成。当暴露于机械应激时,与对照组(p<0.05)和奥沙利铂组(p<0.05)相比,牛磺罗定显著增强了贴壁结肠癌细胞的脱落。这种效应呈剂量依赖性。

结论

除了细胞毒性作用外,牛磺罗定还可以改变癌细胞与环境的机械相互作用。局部癌细胞聚集体可能会被机械动员,并可能导致下游转移生长。牛磺罗定引起的细胞形态变化及其与微环境的相互作用的意义必须在临床癌症治疗中进一步研究。需要进一步的临床研究来评估牛磺罗定治疗腹膜表面恶性肿瘤的安全性和疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa16/9195453/fd2ca94a2a97/40360_2022_572_Fig1_HTML.jpg

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