Chemotherapeutic treatment of squamous cell carcinoma (SCC) of the head and neck has been largely ineffective because of tumor cell resistance. This study examined combinations of cisplatin, 4' demethylepipodophyllotoxin ethylidene D-glucoside (VP-16), and ciprofloxacin, a quinolone antibiotic. VP-16 and ciprofloxacin were used in an effort to inhibit DNA repair and increase cytotoxicity. Chemotherapeutic agents often have a direct damaging effect on cellular DNA. Cytotoxicity may be the result of incomplete DNA repair mechanisms; whereas tumor cell resistance to drugs may be due to efficient DNA recovery. A nuclear enzyme especially important to DNA repair and cell growth is topoisomerase II (topo II). Targeted inhibition of topo II by VP-16 and ciprofloxacin may cause increased cisplatin cytotoxicity. SCC cell lines of head and neck origin were treated with a combination of cisplatin, VP-16, and/or ciprofloxacin with cell viability being assessed by the MTT colorimetric assay. Four of five SCC lines examined demonstrated significant augmentation of cisplatin cytotoxicity with the addition of both VP-16 and ciprofloxacin. These in vitro data suggest methods may exist for improving the chemotherapeutic treatment of SCC of the head and neck.
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