MCF-7和MDA-MB231人乳腺癌细胞在二维和三维培养中的生长和药物反应的比较研究

E. Sefidgar, Shiva Akbari-Birgani
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引用次数: 0

摘要

目的:癌细胞的三维(3D)培养是一种为细胞在三维空间中生长和全面交流提供可能性的方法,从而导致肿瘤球的产生。近年来,利用3D细胞培养方法从癌细胞中建立肿瘤模型引起了人们的广泛关注,因为它作为研究癌症干细胞(cancer stem cells, CSCs)和基于CSCs的治疗方法的一种准确可靠的策略被引入。与细胞的单层培养(二维(2D)培养)相比,三维肿瘤模型更类似于体内条件。因为在肿瘤模型中,肿瘤微环境、细胞间和细胞与细胞外基质的相互作用以及缺氧条件,这些都是CSCs存活所必需的。通过使用几种类型的细胞,包括癌细胞和基质细胞,肿瘤模型有能力发展和反映感兴趣的组织的复杂性,在这种情况下,肿瘤模型在反映身体的生化和物理状况方面更加准确。因此,本研究构建了乳腺癌的三维模型,旨在探讨细胞行为与细胞培养条件(2D和3D)之间的关系,并对两种人类乳腺癌细胞系的生长和药物反应进行比较研究;MCF-7和MDA-MB-231。材料与方法:将MCF-7和MDA-MB-231两种乳腺癌细胞系分别进行二维和三维培养(两种模式;在顶部和嵌入)在基于matrigel的支架上。基于改进剪切变形理论的功能梯度梁表面压电能量收集的细胞分子表型122先进与智能材料力学学报1(2)(2022)121 - 134标记物的流式细胞术检测。观察乳腺球生长12 d,测定其生长动力学。评价两种抗癌药物对细胞的药物反应;放线菌素D和紫杉醇。首先评估两种药物的IC50值,然后按照药物的指示剂量处理生成的乳房微球,并观察其对乳房微球生长的影响。结果:2、3D培养的MCF-7和MDA-MB-231细胞系在分子表型上有显著差异。因此,CD44的表达似乎明显降低。另一方面,细胞在两种不同的三维培养模式下的生长速率;On to和embedded,是不同的。很可能,药物反应评价在2D和3D培养中存在显著差异,因此紫杉醇在3D培养中的抑制作用与放线菌素D相比有所下降。此外,结果表明MCF-7和MDA-MB231具有不同的药物反应,这可能受其不同的分子表型的影响。结论:本研究结果证实了肿瘤细胞的分子表型、生长和药物反应受待研究细胞系类型、细胞培养方法和应用药物的强烈影响。因此,要尽可能准确地进行癌症研究,就需要获得与体内相应肿瘤最相似的模型。هرود،تفابولولس13هرامش،2لاس،1401تاحفص،121ات134
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The comparative study of growth and drug response of MCF-7 and MDA-MB231 human breast cancer cells in two- and three-dimensional culture
Breast cancer, Threedimensional cell culture, Drug response, Molecular phenotype Aim: The three-dimensional (3D) culture of cancer cells is a method that provides the possibility for growth and comprehensive communication of cells in a 3D space, leading to the generation of tumorspheres. In recent years, developing tumor models from cancer cells by using the 3D cell culture method has attracted a lot of attention because it has been introduced as an accurate and reliable strategy for studying cancer stem cells (CSCs) and CSC-based therapeutics. The 3D tumor models in comparison to the monolayer culture (two-dimensional (2D) culture) of cells more resemble in vivo conditions. Because in tumor models, the tumor microenvironment, cell to cell and cell to extracellular matrix interactions and hypoxia condition, which is necessary for the survival of CSCs, are well reproduced. Through the use of several types of cells, including cancer and stromal cells, tumor models have the ability to develop and reflect the complexity of the tissue of interest, which in such a case, are even more accurate models in reflecting the biochemical and physical conditions of the body. Therefore, in the present study, the 3D model of breast cancer has been constructed with the aim of investigating the relationship between the cell behavior and the cell culture conditions (2D and 3D), and a comparative study of the growth and drug response of the two human breast cancer cell lines; MCF-7, and MDA-MB-231. Material and Methods: The two breast cancer cell lines, MCF-7, and MDA-MB-231, were cultured in 2D and 3D (in two modes; on top and embedded) on the Matrigel-based scaffold. The molecular phenotype of cells based on surface Piezoelectric Energy Harvesting from Functionally Graded Beams Using Modified Shear Deformation Theories 122 Mechanics of Advanced and Smart Materials Journal 1(2) (2022) 121– 134 markers was examined by flow cytometry. Mammosphere growth was followed in 12 days and their growth kinetics was determined. To evaluate the drug response of cells, two anticancer drugs; actinomycin D and paclitaxel were applied. Primarily, the IC50 values of the two drugs were evaluated, then the generated mammospheres were treated at the indicated dose of the drugs, and their effect on the growth of the mammospheres was followed. Results: The MCF-7 and MDA-MB-231 cell lines cultured in 2 and 3D, showed a significant difference in their molecular phenotypes. So, it seems that the expression of CD44 has significantly decreased. On the other hand, the growth rate of cells in two different modes of 3D culture; on to and embedded, is different. Likely, the drug response evaluation shows a significant difference in 2D and 3D culture, so that the inhibitory effect of paclitaxel compared to actinomycin D has decreased in 3D culture. In addition, the results show that MCF-7 and MDA-MB231 have different drug responses, which can be affected by their different molecular phenotypes. Conclusion: The results of the study confirm that the molecular phenotype of cancer cells, their growth, and drug response are strongly affected by the type of the understudied cell lines, the cell culture method, and the applied drug. Consequently, conducting cancer studies as accurately as possible requires obtaining a model that is most similar to the corresponding tumor in the body. هرود ،تفاب و لولس 13 هرامش ، 2 لاس ، 1401 تاحفص ، 121 ات 134
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