AUTHOR=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 TITLE=Application of a 3D Bioprinted Hepatocellular Carcinoma Cell Model in Antitumor Drug Research JOURNAL=Frontiers in Oncology VOLUME=10 YEAR=2020 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00878 DOI=10.3389/fonc.2020.00878 ISSN=2234-943X ABSTRACT=

The existing in vitro models for antitumor drug screening have great limitations. Many compounds that inhibit 2D cultured cells do not exhibit the same pharmacological effects in vivo, 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.