Naya El Mokbel , Alicia A. Goyeneche , Rewati Prakash , Benjamin N. Forgie , Farah H. Abdalbari , Xing Zeng , Basile Tessier-Cloutier , Shuk On Annie Leung , Carlos M. Telleria
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引用次数: 0
摘要
高级别浆液性癌是最常见的卵巢癌类型,通常诊断为晚期,由于复发和最终对标准铂类疗法产生耐药性,死亡率很高。本研究的目的是比较二维(2D)和三维(3D)细胞培养作为临床前模型对卡铂、紫杉醇和尼拉帕利的反应,使用的细胞系为 PEO1、PEO4 和 PEO6,这些细胞系由同一患者在疾病进展过程中产生。从形态上看,细胞在二维和三维中分别形成了具有不同压实模式的扁平粘附层和球形结构。二维细胞很少发生凋亡,而三维细胞则形成多层结构,外层为活体增殖细胞,内核为凋亡细胞。此外,在三维细胞系中观察到细胞产生 ATP 的能力不同,而在二维细胞系中则没有。虽然在两种情况下对卡铂、紫杉醇和尼拉帕利的反应趋势相似,但在三维中观察到的敏感性低于二维。总之,三维细胞培养可能更能反映体内细胞的肿瘤行为,也更适合进行治疗评估,因为它增加了二维细胞培养所没有的复杂性。
Comparison of two-dimensional and three-dimensional culture systems and their responses to chemotherapy in cells representing disease progression of high-grade serous ovarian cancer
High-grade serous cancer is the most common type of ovarian cancer and is usually diagnosed at advanced stages with high mortality due to recurrence and eventual resistance to standard platinum therapy. The aim of this study was to compare two-dimensional (2D) versus tridimensional (3D) cell culture as a preclinical model of response to carboplatin, paclitaxel and niraparib using PEO1, PEO4 and PEO6 cell lines, which were generated from the same patient along disease progression. Morphologically, cells formed flat adherent layers versus spheroidal structures with different compaction patterns in 2D and 3D respectively. In 2D, apoptosis was rare whereas in 3D cells formed a multilayered structure with an outer layer of live proliferating cells and an inner core of apoptotic cells. Furthermore, a differential capacity to produce ATP was observed among the cell lines in 3D but not in 2D. While response to carboplatin, paclitaxel and niraparib in both settings followed a similar trend, a lower sensitivity was observed in 3D with respect to 2D. Overall, 3D cell culture is likely more reflective of the in vivo cellular tumor behavior and more suitable of therapeutic evaluation given its added complexity absent in 2D.
期刊介绍:
Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.