Haller J, Burgess R, Dawson D
Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City.
Laryngoscope. 1993 Oct;103(10):1081-3. doi: 10.1288/00005537-199310000-00001.
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.
由于肿瘤细胞耐药，头颈部鳞状细胞癌（SCC）的化疗治疗在很大程度上无效。本研究检测了顺铂、4' -去甲基表鬼臼毒素乙叉甙（VP - 16）和喹诺酮类抗生素环丙沙星的联合使用情况。使用VP - 16和环丙沙星是为了抑制DNA修复并增强细胞毒性。化疗药物通常对细胞DNA有直接损伤作用。细胞毒性可能是DNA修复机制不完全的结果；而肿瘤细胞对药物的耐药性可能是由于有效的DNA修复。一种对DNA修复和细胞生长特别重要的核酶是拓扑异构酶II（topo II）。VP - 16和环丙沙星对topo II的靶向抑制可能会增强顺铂的细胞毒性。对头颈部来源的SCC细胞系用顺铂、VP - 16和/或环丙沙星联合处理，并通过MTT比色法评估细胞活力。所检测的五个SCC细胞系中有四个显示，添加VP - 16和环丙沙星后顺铂的细胞毒性显著增强。这些体外数据表明，可能存在改善头颈部SCC化疗治疗的方法。
