Biophysical Society Thematic Meeting

Mechanobiology of Disease

Poster Abstracts

43-POS

Board 43

3D-image-based Assays of Drug Combination Efficacy on Cancer Cell and Fibroblast

Co-culture Spheroids

Chau-Hwang Lee

1,2,3

, Yi-Hao Chen

, Yu-Fang Hsiao

, Yi-Chung Tung

Academia Sinica, Taipei, Taiwan,

National Yang-Ming University, Taipei, Taiwan,

National

Taiwan University, Taipei, Taiwan.

Objective: We proposed to use cancer cell and fibroblast co-culture spheroids as a platform to

evaluate the efficacy of anti-cancer drug combinations. Selective-plane illumination microscopy

(SPIM) was employed to provide a 3D perspective of relative positions of the co-cultured cells.

Results: We found that the co-culture of CL1-0 lung cancer cells and MRC-5 fibroblasts could

form a spheroid (diameter ~ 200 µm) much easier than the cancer cell alone. Regardless of the

seeding sequence, the fibroblasts were enclosed by the cancer cells in a spheroid. In contrast,

while the cancer cells were co-cultured with bronchial epithelial cells, the latter did not invade

into the cancer cell aggregation. This result implied that fibroblasts could play an essential role in

the early stage of tumor development.

Next, we used the co-culture spheroids to test the efficacy of an anti-cancer drug erlotinib in

combination with chloroquine, the inhibitor of cellular autophagy. With the SPIM images, we

found that the survival rate of cancer cells in the co-culture spheroids was much higher than that

of cells in cancer-cell spheroids under the treatment of 10 µM erlotinib. In addition, the

combination of 10 µM erlotinib and 20 µM chloroquine showed a high efficacy in killing the

cancer cells in the co-culture spheroids. In contrast, in the 2D co-culture of lung cancer cells and

fibroblasts, 10 µM erlotinib alone showed a much higher efficacy in killing the cancer cells.

Conclusion: In this work we demonstrated that cancer cell and fibroblast co-culture spheroids

combined with 3D imaging could serve as a useful platform to investigate the tumor formation

process and to test the drug combination efficacy. The 3D microenvironment could be an

important factor that must be included in the evaluation of therapeutic strategies.