Reproduction of the Antitumor Effect of Cisplatin and Cetuximab Using a Three-dimensional Spheroid Model in Oral Cancer.
Reproduction of the Antitumor Effect of Cisplatin and Cetuximab Using a Three-dimensional Spheroid Model in Oral Cancer.
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DOI：
10.7150/ijms.74109
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发表时间：
2022
影响因子：
3.6
通讯作者：
Sasaki, Akira
中科院分区：
文献类型：
--
作者：
Ono, Kisho;Sato, Kohei;Nakamura, Tomoya;Yoshida, Yume;Murata, Shogo;Yoshida, Kunihiro;Kanemoto, Hideka;Umemori, Koki;Kawai, Hotaka;Obata, Kyoichi;Ryumon, Shoji;Hasegawa, Kazuaki;Kunisada, Yuki;Okui, Tatsuo;Ibaragi, Soichiro;Nagatsuka, Hitoshi;Sasaki, Akira
背景/目的：肿瘤研究已将培养细胞作为药物发现测试的一部分，但传统的二维培养方法无法反映复杂的肿瘤微环境。另一方面，三维培养最近引起了人们的关注，因为它更接近于体内生理环境的体外模型。本研究的目的是建立一种口腔癌三维培养方法，并验证其实用性。材料和方法：用几种口腔癌细胞系进行三维培养。收集的细胞团（球体）采用Western blotting进行蛋白表达分析，H-E染色进行结构观察。将培养物暴露于顺铂和西妥昔单抗中，比较球体随时间的形态变化和靶蛋白的表达变化。结果：各细胞系形成球状细胞聚集体，细胞黏附分子随时间增强。H-E染色显示每个细胞系特有的肿瘤组织样结构。顺铂在各细胞系中表现出浓度依赖性的抗肿瘤作用，这是由于细胞粘附丧失和球体破坏，而西妥昔单抗在各细胞系中表现出与EGFR表达相关的抗肿瘤作用。结论：口腔癌细胞系形成的球状体具有肿瘤样特征，可能反映了其临床意义。在未来，有可能从口腔癌患者的组织样本中产生肿瘤球体，并将其应用于药物筛选和开发个性化的诊断和治疗方法。
Background/Aim: Cancer research has been conducted using cultured cells as part of drug discovery testing, but conventional two-dimensional culture methods are unable to reflect the complex tumor microenvironment. On the other hand, three-dimensional cultures have recently been attracting attention as in vitro models that more closely resemble the in vivo physiological environment. The purpose of this study was to establish a 3D culture method for oral cancer and to verify its practicality. Materials and Methods: Three-dimensional cultures were performed using several oral cancer cell lines. Western blotting was used for protein expression analysis of the collected cell masses (spheroids), and H-E staining was used for structural observation. The cultures were exposed to cisplatin and cetuximab and the morphological changes of spheroids over time and the expression changes of target proteins were compared. Results: Each cell line formed spheroidal cell aggregates and showed enhancement of cell adhesion molecules over time. H-E staining showed tumor tissue-like structures specific to each cell line. Cisplatin showed concentration-dependent antitumor effects due to loss of cell adhesion and spheroid disruption in each cell line, while cetuximab exhibited antitumor effects that correlated with EGFR expression in each cell line. Conclusion: Spheroids made from oral cancer cell lines appeared to have tumor-like characteristics that may reflect their clinical significance. In the future, it may become possible to produce tumor spheroids from tissue samples of oral cancer patients, and then apply them to drug screening and to develop individualized diagnostic and treatment methods.
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影响因子：
3
作者：
Gu J;Yin L;Wu J;Zhang N;Huang T;Ding K;Cao H;Xu L;He X
通讯作者：
He X
影响因子：
3.7
作者：
Eguchi T;Sogawa C;Okusha Y;Uchibe K;Iinuma R;Ono K;Nakano K;Murakami J;Itoh M;Arai K;Fujiwara T;Namba Y;Murata Y;Ohyama K;Shimomura M;Okamura H;Takigawa M;Nakatsura T;Kozaki KI;Okamoto K;Calderwood SK
通讯作者：
Calderwood SK
影响因子：
5.6
作者：
Gambara G;Gaebler M;Keilholz U;Regenbrecht CRA;Silvestri A
通讯作者：
Silvestri A
影响因子：
64.5
作者：
Gao D;Vela I;Sboner A;Iaquinta PJ;Karthaus WR;Gopalan A;Dowling C;Wanjala JN;Undvall EA;Arora VK;Wongvipat J;Kossai M;Ramazanoglu S;Barboza LP;Di W;Cao Z;Zhang QF;Sirota I;Ran L;MacDonald TY;Beltran H;Mosquera JM;Touijer KA;Scardino PT;Laudone VP;Curtis KR;Rathkopf DE;Morris MJ;Danila DC;Slovin SF;Solomon SB;Eastham JA;Chi P;Carver B;Rubin MA;Scher HI;Clevers H;Sawyers CL;Chen Y
通讯作者：
Chen Y
影响因子：
4.6
作者：
Huetz, Katharina;Zeiler, Julian;Spindler, Volker
通讯作者：
Spindler, Volker