Novel 3-D cell culture system for in vitro evaluation of anticancer drugs under anchorage-independent conditions.
Novel 3-D cell culture system for in vitro evaluation of anticancer drugs under anchorage-independent conditions.
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DOI：
10.1111/cas.13095
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发表时间：
2016-12
期刊：
影响因子：
5.7
通讯作者：
Nishino T
中科院分区：
文献类型：
--
作者：
Aihara A;Abe N;Saruhashi K;Kanaki T;Nishino T
抗癌药物发现工作使用了基于细胞的二维分析模型，该模型无法预测体内疗效，导致临床批准的成功率较低。最近的3-D细胞培养模型有望弥合2-D和体内模型之间的差距。然而，可用于实际抗癌药物筛选的3D细胞培养方法尚未完全实现。在这项研究中，我们筛选了几种聚合物的能力，悬浮细胞或细胞球状体均匀地在液体培养基中，而不改变粘度行为，并确定结冷胶（FP 001），作为最有效的聚合物。FP 001通过抑制大尺寸球状体的形成，促进细胞在培养基中的分散，并在低附着条件下改善多种癌细胞系的增殖。此外，用含FP 001的培养基培养的癌细胞比在附着条件下培养的癌细胞更容易受到表皮生长因子（EGF）信号传导抑制剂的影响。我们还表明，EGF受体家族的配体在使用FP 001的非锚定条件下明显增强SKOV 3卵巢癌细胞的增殖。与该结果一致，与在附着条件下培养的细胞相比，用FP 001生长的细胞显示出更高的EGF受体含量。总之，我们开发了一种新的三维细胞培养系统，可用于抗癌药物的高通量筛选，并适用于分子靶向抗癌药物的评价。使用FP 001的三维细胞培养将在抗癌药物发现的有用技术的开发中具有价值。
Anticancer drug discovery efforts have used 2‐D cell‐based assay models, which fail to forecast in vivo efficacy and result in a lower success rate of clinical approval. Recent 3‐D cell culture models are expected to bridge the gap between 2‐D and in vivo models. However, 3‐D cell culture methods that are available for practical anticancer drug screening have not yet been fully attained. In this study, we screened several polymers for their ability to suspend cells or cell spheroids homogeneously in a liquid medium without changing the viscosity behavior, and identified gellan gum (FP001), as the most potent polymer. FP001 promoted cell dispersion in the medium and improved the proliferation of a wide range of cancer cell lines under low attachment conditions by inhibiting the formation of large‐sized spheroids. In addition, cancer cells cultured with FP001‐containing medium were more susceptible to inhibitors of epidermal growth factor (EGF) signaling than those cultured under attachment conditions. We also showed that ligands of the EGF receptor family clearly enhance proliferation of SKOV3 ovarian carcinoma cells under anchorage‐independent conditions with FP001. Consistent with this result, the cells grown with FP001 showed higher EGF receptor content compared with cells cultured under attachment conditions. In conclusion, we developed a novel 3‐D cell culture system that is available for high throughput screening of anticancer agents, and is suitable for evaluation of molecular‐targeted anticancer drugs. Three‐dimensional cell culture using FP001 will be of value in the development of useful technologies for anticancer drug discovery.
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影响因子：
3.8
作者：
Longati P;Jia X;Eimer J;Wagman A;Witt MR;Rehnmark S;Verbeke C;Toftgård R;Löhr M;Heuchel RL
通讯作者：
Heuchel RL
影响因子：
8
作者：
Amundadottir, LT;Leder, P
通讯作者：
Leder, P
DOI：
10.1165/rcmb.2008-0320oc
发表时间：
2009-07-01
影响因子：
6.4
作者：
Yang, Tsung-Ming;Barbone, Dario;Broaddus, V. Courtney
通讯作者：
Broaddus, V. Courtney
影响因子：
7.5
作者：
Frisch, SM;Ruoslahti, E
通讯作者：
Ruoslahti, E
SGEF 通过延迟 EGFR 从早期内体到晚期内体的运输来增强 EGFR 稳定性。
影响因子：
4.7
作者：
Wang, Hongtao;Li, Shanhu;Zhou, Jianguang
通讯作者：
Zhou, Jianguang