Background: The promising results of anticancer drug screening on monolayer cultures are often poorly reproduced in vivo models. The use of clinically relevant three-dimensional in vitro models of human tumors, such as spheroids, for the assessment of antitumor efficacy offers a more robust platform for drug testing. This may be especially crucial for drugs that target cellular metabolism.
Aim: To comparative study of the antitumor activity of methionine–γ-lyase (MGL) on 2D and 3D models of human tumors
Methods: To evaluate the cytotoxicity of MGL, human fibroblast cell culture and tumour cell lines of human breast cancer (MCF7), colorectal cancer (HCT-116), human pancreatic cancer (PANC-1), liver cancer (Huh7) and human prostate cancer (LNCaP) were employed. Culture plates with a low adhesive coating were utilised to fabricate spheroids. Cell survival was assessed using a resazurin test.
Results: In the spheroid model, cell survival after 72 hours of MGL treatment was observed to be higher than in the monolayer culture model in all tested cell cultures. The lowest sensitivity to the effects of MGL was observed in fibroblasts in both the 2D and 3D cultivation models, with IC50 values of 2.2 and 9.1 ME/ml, respectively. The most sensitive cell cultures to MGL were the rapidly proliferating PANC-1 and HCT-116 cells in both 2D and 3D models, with IC50 values of 0.23 and 1.5 IU/ml and 0.83 and 1.43 IU/ml, respectively.
Conclusion: The effect of MGL on cell survival in spheroids is less pronounced than in a monolayer. Cell survival in spheroids exposed to MGL did not depend on spheroid size or growth rate. Despite the fact that the maximum cytotoxic effect on spheroids was obtained in the rapidly growing HCT-116 colon cancer model and the lowest in the slowly dividing fibroblast model, this dependence is not so obvious in other cell types. In general, the spheroid model has proved useful for testing specific activity of enzymatic antitumor drugs, avoiding the hypersensitivity of monolayer cancer models.
