3D fluorescence imaging observations of the drug efficacy on co-culture tumor spheroids

• Main Authors: Yi-Hao Chen, 陳一豪
• Other Authors: Chau-Hwang Lee
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/89527283462549959846

碩士 === 國立陽明大學 === 生醫光電研究所 === 104 === Abstract In recent research, the interactions between cancer cells and cancer-associated fibroblasts are recognized as potential therapeutic targets. However, animal studies on relevant research are expensive and cumbersome, thus, there are more and more research using 3D spheroid as their model. In contrast to traditional 2D monolayer cultures, which lack the architecture and specific organization, 3D spheroid culture systems better mimic the in vivo tumor tissue. We used Bessel beam selective plane illumination microscopy (Bessel beam SPIM) to observe the interaction between fibroblasts and lung cancer cells in a co-culture spheroid in microfluidic device. We found that the fibroblasts aggregated into the center of a co-culture spheroid, and further attracted the cancer cells’ attaching. In contrast to this behavior of fibroblast, the bronchial epithelial cells stayed around the periphery of a tumor spheroid. This result was confirmed with time-lapse imaging by Bessel beam SPIM. Drug resistance is correlated with the autophagy occurred in tumor stromal cells. We also conducted the assay of drug combination tests in this co-culture spheroid model. With the inhibitor of cellular autophagy, the enhanced efficacy of erlotinib (Tarceva®) for killing the lung cancer cells were confirmed with cell viability assay and Bessel beam SPIM. Furthermore, the comparison between 2D and 3D cultures indicated that the drug efficacy was impaired due to the limited flow of drug into the core in 3D culture. These results agree with the results of animal tests reported in the literature.