Sun Lejia, Yang Huayu, Wang Yanan, Zhang Xinyu, Jin Bao, Xie Feihu, Jin Yukai, Pang Yuan, Zhao Haitao, Lu Xin, Sang Xinting, Zhang Hongbing, Lin Feng, Sun Wei, Huang Pengyu, Mao Yilei
Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, China.
State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, CAMS and School of Basic Medicine, PUMC, Beijing, China.
Front Oncol. 2020 Jun 3;10:878. doi: 10.3389/fonc.2020.00878. eCollection 2020.
The existing models for antitumor drug screening have great limitations. Many compounds that inhibit 2D cultured cells do not exhibit the same pharmacological effects , thereby wasting human and material resources as well as time during drug development. Therefore, developing new models is critical. The 3D bioprinting technology has greater advantages in constructing human tissue compared with sandwich culture and organoid construction. Here, we used 3D bioprinting technology to construct a 3D model with HepG2 cells (3DP-HepG2). The biological activities of the model were evaluated by immunofluorescence, real-time quantitative PCR, and transcriptome sequencing. Compared with the traditional 2D cultured tumor cells (2D-HepG2), 3DP-HepG2 showed significantly improved expression of tumor-related genes, including ALB, AFP, CD133, IL-8, EpCAM, CD24, and β-TGF genes. Transcriptome sequencing analysis revealed large differences in gene expression between 3DP-HepG2 and 2D-HepG2, especially genes related to hepatocyte function and tumor. We also compared the effects of antitumor drugs in 3DP-HepG2 and 2D-HepG2, and found that the large differences in drug resistance genes between the models may cause differences in the drugs' pharmacodynamics.
现有的抗肿瘤药物筛选模型存在很大局限性。许多能抑制二维培养细胞的化合物并未表现出相同的药理作用，从而在药物研发过程中浪费了人力、物力和时间。因此，开发新模型至关重要。与三明治培养和类器官构建相比，三维生物打印技术在构建人体组织方面具有更大优势。在此，我们使用三维生物打印技术构建了含HepG2细胞的三维模型（3DP - HepG2）。通过免疫荧光、实时定量PCR和转录组测序对该模型的生物学活性进行了评估。与传统二维培养的肿瘤细胞（2D - HepG2）相比，3DP - HepG2中包括ALB、AFP、CD133、IL - 8、EpCAM、CD24和β - TGF基因在内的肿瘤相关基因表达显著提高。转录组测序分析显示3DP - HepG2和2D - HepG2之间的基因表达存在很大差异，尤其是与肝细胞功能和肿瘤相关的基因。我们还比较了抗肿瘤药物在3DP - HepG2和2D - HepG2中的作用，发现模型之间耐药基因的巨大差异可能导致药物药效动力学的差异。
