Cancer cells growing on perfused 3D collagen model produced higher reactive oxygen species level and were more resistant to cisplatin compared to the 2D model

Abstract

Introduction: Three-dimensional (3D) collagen scaffold models, due to their ability to mimic the tissue and organ structure in vivo, have received increasing interest in drug discovery and toxicity evaluation. Methods: In this study, we developed a perfused 3D model and studied cellular response to cytotoxic drugs in comparison with traditional 2D cell cultures as evaluated by cancer drug cisplatin. Results: Cancer cells grown in perfused 3D environments showed increased levels of reactive oxygen species (ROS) production compared to the 2D culture. As determined by growth analysis, cells in the 3D culture, after forming a spheroid, were more resistant to the cancer drug cisplatin compared to that of the 2D cell culture. In addition, 3D culturing cells showed elevated level of ROS, indicating a physiological change or the formation of a microenvironment that resembles tumor cells in vivo. Conclusions: These data revealed that cellular response to drugs for cells growing in 3D environments are dramatically different from that of 2D cultured cells. Thus, the perfused 3D collagen scaffold model we report here might be a potentially very useful tool for drug analysis.

Concentration-Dependent Pro- and Antitumor Activities of Quercetin in Human Melanoma Spheroids: Comparative Analysis of 2D and 3D Cell Culture Models

“…Again, a high concentration further increased the ROS production, whereas low concentrations (1 µM) diminished this effect, suggesting that the anti-and pro-oxidative activity of quercetin is concentration-dependent. Recently, it was demonstrated that 3D-grown cancer cells showed increased levels of ROS production, compared to 2D cultures, and that moderate ROS levels promote cell survival and proliferation [38,39]. Nrf-2 analysis revealed a concentration-dependent increase of Nrf2 reporter activity and corresponding transcriptional targets, SOD2, NQO1, GCLC, and HmMOX1, in MCM DLN spheroids when treated with quercetin for 24 h, compared to the control (Figure 6).…”

Gastric Organoids: Progress and Remaining Challenges

“… 80 For example, a recent study using organoids derived from human breast cancer showed higher levels of reactive oxygen species production and increased resistance to cisplatin compared with standard 2D cell cultures. 81 Importantly, organoids have been shown to exhibit different drug metabolism and secretion properties due to their different environmental cues, making them well suited for the study of drug therapies. 80 Because organoids more accurately represent human disease, they have tremendous potential for predicting in vivo drug sensitivity and responses.…”

Cytotoxicity evaluation of sodium lauryl sulfate in a paper-based 3D cell culture system

“…We next compared the cytotoxicity of SLS between our new paper-based 3D cell culture platform and a commercialized 3D cell culture kit. In the commercially available 3D cell culture kit containing collagen-rich ECM, the cells grew into a circular form, 47,48 and on the paper-based 3D cell culture platform, the cells attached to and diffused across the surface in response to its topographical features (Fig. 4B).…”