Auchter R M, Pickart M A, Nash G A, Qu R P, Harari P M
Department of Human Oncology, University of Wisconsin, Madison, USA.
Arch Otolaryngol Head Neck Surg. 1996 Sep;122(9):977-81. doi: 10.1001/archotol.1996.01890210051012.
The capacity of radiation to cure advanced head and neck squamous cell carcinoma is compromised by the proliferation of surviving tumor cells during the course of therapy (overall duration, often 7-9 weeks). Antiproliferative agents that inhibit tumor proliferation, even in the absence of direct cytotoxicity, may be useful adjuncts for concurrent use with radiation. Modulation of endogenous polyamine (PA) metabolism has the potential to inhibit cell growth. The PA analogue 1,19-bis(ethylamino)-5,10,15-triazanonadecane (BE 4444) is a synthetic compound that demonstrates antiproliferative effects in human tumor cells.
To evaluate the PA analogue BE 4444 for its inhibitory effect on the growth of human squamous cell carcinoma xenografts in nude mice.
Xenografts of human squamous cell carcinomas were grown in nude mice; then, BE 4444 was injected intraperitoneally (5 mg/kg) on a twice-daily schedule for 8 days. Tumor growth measurements were performed twice weekly for 8 weeks and compared with those of control mice that were injected with sterile saline solution on the same schedule. The PA levels in the tumor and normal tissue samples were assayed at the completion of treatment.
Tumor volume in the BE 4444-treated mice was reduced by 62% compared with tumor volumes in control mice, and the tumor growth rate was reduced by 64%. This growth inhibition was maintained through completion of the experiment. Levels of endogenous PAs were not significantly different from control levels, suggesting that the mechanism of action for BE 4444 is not simply PA biosynthesis inhibition.
The PA analogue BE 4444 is an inhibitor of human squamous cell cancer growth. Further studies are in progress to characterize the potential value of PA analogues as adjuncts to radiation therapy for rapidly proliferating squamous cell carcinoma of the head and neck.
在治疗过程中（总疗程通常为7 - 9周），存活肿瘤细胞的增殖会削弱放疗治愈晚期头颈部鳞状细胞癌的能力。即使在没有直接细胞毒性的情况下，抑制肿瘤增殖的抗增殖剂也可能是与放疗联合使用的有用辅助药物。调节内源性多胺（PA）代谢具有抑制细胞生长的潜力。PA类似物1,19 - 双（乙氨基）- 5,10,15 - 三氮杂十九烷（BE 4444）是一种在人类肿瘤细胞中表现出抗增殖作用的合成化合物。
评估PA类似物BE 4444对裸鼠人鳞状细胞癌异种移植瘤生长的抑制作用。
将人鳞状细胞癌异种移植瘤接种于裸鼠；然后，以每日两次的给药方案腹腔注射BE 4444（5毫克/千克），共8天。在8周内每周两次测量肿瘤生长情况，并与按相同方案注射无菌盐溶液的对照小鼠进行比较。治疗结束时测定肿瘤和正常组织样本中的PA水平。
与对照小鼠的肿瘤体积相比，BE 4444治疗组小鼠的肿瘤体积减少了62%，肿瘤生长速率降低了64%。这种生长抑制在实验结束时一直保持。内源性PA水平与对照水平无显著差异，提示BE 4444的作用机制并非简单的PA生物合成抑制。
PA类似物BE 4444是人类鳞状细胞癌生长的抑制剂。目前正在进行进一步研究，以确定PA类似物作为头颈部快速增殖鳞状细胞癌放疗辅助药物的潜在价值。
