A rapid in vitro screening system for the identification and evaluation of anticancer drugs.
We report the development of an in vitro screening system that can be used to identify new anticancer drugs that are specifically cytotoxic for dividing cells. The screening system takes advantage of the potential of many cell lines, including tumor cells, to stop dividing when they are plated at high cell density. The cytotoxic effects of anticancer drugs on dividing (i.e., cells plated at low cell density) and nondividing cells (i.e., cells plated at high cell density) is measured by the incorporation of 51Cr. This in vitro system was evaluated by measuring the cytotoxic effects of the anticancer drugs cisplatin, thiotepa, doxorubicin, methotrexate, and vinblastine on the cell lines B/C-N, ME-180, and MCF-7. In this in vitro system the concentrations of the anticancer drugs that produced significant cytotoxicity on only dividing cells are similar to the concentrations that are used clinically. The fact that this in vitro system is rapid, simple, applicable to many cell types, and able to predict effective concentrations of anticancer drugs should make it useful for the screening of new anticancer drugs and for the design of preclinical studies.
Kao
J W
JW
Washington University School of Medicine, St. Louis, Missouri 63110.
Collins
J L
JL
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002860:Chromium Radioisotopes; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D002860:Chromium Radioisotopes; D013936:Thymidine