Modulation of Proliferation Kinetics in Human Squamous Cell Carcinomas of the Head and Neck

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Abstract
Proliferation of tumor clonogens during a course of conventional head and neck radiotherapy serves to compromise ultimate tumor control. Biologic strategies that attempt to alter tumor proliferation kinetics using cytostatic or antiproliferative agents may therefore prove valuable by limiting tumor cell repopulation during therapy. Three human squamous cell carcinoma (SCC) cell lines, derived from primary head and neck cancers, have been characterized in vitro via flow cytometric analysis of proliferation kinetics, and in vivo via tumor xenograft growth evaluation in athymic mice. The antiproliferative agent alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, induced growth inhibition of these SCCs in culture and when administered orally to athymic mice harboring SCC tumor xenografts. Cell cycle kinetic analysis via flow cytometry revealed that DFMO induced a lengthening of in vitro tumor cell potential doubling times. Similarly, DFMO administered continuously via the drinking water to athymic mice harboring human SCC xenografts induced a prolongation of in vivo tumor volume doubling. These data indicate that biologic agents, such as DFMO, can alter SCC growth kinetics and may prove useful in designing new therapeutic strategies for rapidly proliferating tumors such as those that occur in the head and neck.