Three dimensional cultivation increases chemo- and radioresistance of colorectal cancer cell lines.
Three dimensional cultivation increases chemo- and radioresistance of colorectal cancer cell lines.
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DOI：
10.1371/journal.pone.0244513
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Renner P
中科院分区：
文献类型：
--
作者：
Koch J;Mönch D;Maaß A;Gromoll C;Hehr T;Leibold T;Schlitt HJ;Dahlke MH;Renner P
尽管2D细胞培养通常用于预测治疗反应，但3D培养显然可能更好地模拟体内情况，并提供量身定制转化型临床方法的可能性。在这里，我们比较了2D和3D结直肠癌(CRC)细胞系对放射和化疗的反应。建立经典的结直肠癌细胞系(CaCo2、Colo205、HCT116、SW480)的2D培养和3D球体，然后用临床级直线加速器进行1、4、10Gy射线照射。通过免疫组织化学、流式细胞仪和TUNEL检测来评估反应。照射后，CRC3D球体形态发生改变。经10Gy射线照射后，Annexin V/PI染色显示2D细胞凋亡率增加1.8~4倍(95%CI 3.24±0.96)，3D球体细胞凋亡率增加1.5~2.4倍(95%CI 1.56±0.41)。1Gy射线照射后，二维培养的CaCO2和HCT116(p=0.01)的TUNEL阳性细胞数分别增加了3倍和4倍，而三维球形培养的细胞数则增加了2倍。此外，2D和3D细胞对化疗的反应不同，3D细胞对5-FU和顺铂的耐药性高于2D细胞，而对阿霉素和丝裂霉素C的耐药性不明显。综上所述，培养为3D球体的CRC细胞对放射治疗和化疗药物的耐受性明显高于2D培养细胞。在未来的方法中，必须考虑这种体外差异，以确定模仿人类疾病的理想体外系统。
Although 2D cell cultures are commonly used to predict therapy response, it has become clear that 3D cultures may better mimic the in vivo situation and offer the possibility of tailoring translational clinical approaches. Here, we compared the response of 2D and 3D colorectal cancer (CRC) cell lines to irradiation and chemotherapy. Classic 2D cultures and 3D spheroids of CRC cell lines (CaCo2, Colo205, HCT116, SW480) were thoroughly established, then irradiated with doses of 1, 4, or 10 Gy, using a clinical-grade linear accelerator. The response was assessed by immunohistochemistry, flow cytometry, and TUNEL assays. Upon irradiation, CRC 3D spheroids were morphologically altered. After irradiation with 10 Gy, annexin V/PI staining revealed a 1.8- to 4-fold increase in the apoptosis rate in the 2D cell cultures (95% CI 3.24±0.96), and a 1.5- to 2.4-fold increase in the 3D spheroids (95% CI 1.56±0.41). Irradiation with 1 Gy caused 3- and 4-fold increases in TUNEL positive cells in the CaCo2 and HCT116 (p = 0.01) 2D cultures, respectively, compared with a 2-fold increase in the 3D spheroids. Furthermore, the 2D and 3D cultures responded differently to chemotherapy; the 3D cultures were more resistant to 5-FU and cisplatin, but not to doxorubicin and mitomycin C, than the 2D cultures. Taken together, CRC cells cultured as 3D spheroids displayed markedly higher resistance to irradiation therapy and selected chemotherapeutic drugs than 2D cultures. This in vitro difference must be considered in future approaches for determining the ideal in vitro systems that mimic human disease.
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分析两个辐照的肿瘤球体模型中的辐射效应。
影响因子：
2.9
作者：
Al-Ramadan A;Mortensen AC;Carlsson J;Nestor MV
通讯作者：
Nestor MV
影响因子：
16
作者：
Xu, Xian;Farach-Carson, Mary C.;Jia, Xinqiao
通讯作者：
Jia, Xinqiao
DOI：
10.1016/j.jconrel.2012.04.045
发表时间：
2012-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Mehta G;Hsiao AY;Ingram M;Luker GD;Takayama S
通讯作者：
Takayama S
患者来源的类器官预测局部晚期直肠癌的放化疗反应
影响因子：
23.9
作者：
Yao, Ye;Xu, Xiaoya;Hua, Guoqiang
通讯作者：
Hua, Guoqiang
影响因子：
3.4
作者：
Cannon, T. M.;Shah, A. T.;Skala, M. C.
通讯作者：
Skala, M. C.