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Development and cytotoxic response of two proliferative MDA- MB-231 and non-proliferative SUM1315 three-dimensional cell culture models of triple-negative basal-like breast cancer cell lines

机译:两种增殖性mDa-mB-231和两种增殖剂的发育和细胞毒性反应   非增殖性sUm1315三维细胞培养模型   三阴性基底样乳腺癌细胞系

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摘要

Triple-Negative Basal-Like tumors, representing 15 to 20% of breast cancers,are very aggressive and with poor prognosis. Targeted therapies have beendeveloped extensively in preclinical and clinical studies to open the way fornew treatment strategies. The present study has focused on developing 3D cellcultures from SUM1315 and MDA-MB-231, two triple-negative basal-like (TNBL)breast cancer cell lines, using the liquid overlay technique. Extracellularmatrix concentration, cell density, proliferation, cell viability, topology andultrastructure parameters were determined. The results showed that for bothcell lines, the best conditioning regimen for compact and homogeneous spheroidformation was to use 1000 cells per well and 2% Geltrex. This conditioningregimen highlighted two 3D cell models: non-proliferative SUM1315 spheroids andproliferative MDA-MB-231 spheroids. In both cell lines, the comparison of 2D vs3D cell culture viability in the presence of increasing concentrations ofchemotherapeutic agents i.e. cisplatin, docetaxel and epirubicin, showed thatspheroids were clearly less sensitive than monolayer cell cultures. Moreover, aproliferative or non-proliferative 3D cell line property would enabledetermination of cytotoxic and/or cytostatic drug activity. 3D cell culturecould be an excellent tool in addition to the arsenal of techniques currentlyused in preclinical studies. http://www.impactjournals.com/oncotarget/Oncotarget, Advance Publications 2017
机译:三阴性基底样肿瘤占乳腺癌的15%至20%,侵袭性强,预后差。在临床前和临床研究中已经广泛开发了靶向疗法,为新的治疗策略开辟了道路。本研究集中于利用液体覆盖技术,从SUM1315和MDA-MB-231这两种三阴性基础样(TNBL)乳腺癌细胞系开发3D细胞培养。测定细胞外基质浓度,细胞密度,增殖,细胞活力,拓扑和超结构参数。结果表明,对于两种细胞系,紧凑而均匀的球体形成的最佳条件是每孔使用1000个细胞和2%的Geltrex。此调理方案重点介绍了两个3D细胞模型:非增殖SUM1315椭球和增殖MDA-MB-231椭球。在两种细胞系中,在增加浓度的化学治疗剂(即顺铂,多西紫杉醇和表柔比星)存在下,2D与3D细胞培养物活力的比较表明,球体显然不如单层细胞培养物敏感。而且,增殖或非增殖3D细胞系特性将能够确定细胞毒性和/或抑制细胞的药物活性。除了目前临床前研究中使用的技术外,3D细胞培养可能是一种出色的工具。 http://www.impactjournals.com/oncotarget/Oncotarget,高级出版物2017

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