Are syngeneic mouse tumor models still valuable experimental models in the field of anti-cancer drug discovery?
To establish the pharmacological profile of a molecule with anti-cancer potential, it seems essential to add an in vivo approach to the first pharmacological experiments carried out in vitro. The present study aims to characterize the degree of sensitivity of seven syngeneic models (two leukemias and five solid tumors) to eleven molecules which have proven to be clinically reliable. We also used some of these models to investigate whether the molecular effects on the extent of growth in a subcutaneously grafted experimental model correlate with the effects of the same drug on the survival of the animals so grafted. Our data show that all the molecules demonstrated significant anti-tumor activities in two mouse leukemia models (with some discrepancies between the two). Two lymphoma models displayed weaker chemosensitivity profiles than the two leukemia models from which they were developed. Two other models, namely the MXT-HS mammary carcinoma and the B16 melanoma, appeared to be rather chemoresistant. However, a direct relationship was evident between the drug-induced decrease in the tumor growth rate and the increase observed in the survival periods of the MXT tumor-bearing mice. This relationship was also observed in the L1210_LYM lymphoma, though to a lesser extent, and was completely absent from the B16 melanoma model. Finally, our data indicated that we had developed a pair of metastasizing, as opposed to non-metastasizing, lymphoma and mammary carcinoma models. In conclusion, the present study shows that syngeneic mouse tumor models can be used as valuable in vivo experimental models for the screening of potential anti-cancer agents.
Darro
Francis
F
Unibioscreen SA, 1070 Brussels, Belgium.
Decaestecker
Christine
C
Gaussin
Jean-François
JF
Mortier
Steven
S
Van Ginckel
Rob
R
Kiss
Robert
R
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000379:methods* / Q000706:statistics & numerical data; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology; D007941:Leukemia P388 / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D015203:Reproducibility of Results
D000970:Antineoplastic Agents