Department of Medicine, University of California, San Diego, La Jolla, Calif., and Veterans Medical Research Foundation, San Diego, CA 92093-0676, USA.
Chemotherapy. 2010;56(1):54-9. doi: 10.1159/000292582. Epub 2010 Mar 8.
BACKGROUND/AIMS: 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG) is one of the most active antiproliferative compounds in a series of acyclic nucleoside phosphonates and is active in intraperitoneal P388 tumors in mice.
We synthesized octadecyloxyethyl (ODE) and hexadecyloxypropyl esters of PMEG and compared their antiproliferative activity with unmodified PMEG in primary human fibroblasts and CaSki, Me-180 and HeLa human cervical cancer cell lines in vitro.
ODE-PMEG had excellent antiproliferative activity in vitro in this panel of human cervical cancers. We compared the effects of ODE-PMEG and ODE-cidofovir (ODE-CDV) in a solid tumor model using Me-180 human cervical cancer cell lines in athymic nude mice. Intratumoral injection of 25 microg of ODE-PMEG or 100 microg of ODE-CDV daily for 21 days followed by observation for 20-35 days resulted in near-complete disappearance of measurable cervical cancers.
ODE-PMEG may be suitable for local or topical treatment of cervical dysplasia.
背景/目的：9-[2-(膦酸甲氧基)乙基]鸟嘌呤（PMEG）是无环核苷膦酸酯系列中最具活性的抗增殖化合物之一，对小鼠腹腔内 P388 肿瘤具有活性。
我们合成了 PMEG 的十八烷氧基乙基（ODE）和十六烷氧基丙基酯，并在体外比较了它们在原代人成纤维细胞和 CaSki、Me-180 和 HeLa 人宫颈癌细胞系中的抗增殖活性与未修饰的 PMEG。
在该组人宫颈癌中，ODE-PMEG 具有极好的体外抗增殖活性。我们在裸鼠中使用 Me-180 人宫颈癌细胞系的实体瘤模型比较了 ODE-PMEG 和 ODE-更昔洛韦（ODE-CDV）的作用。连续 21 天每天瘤内注射 25μg ODE-PMEG 或 100μg ODE-CDV，然后观察 20-35 天，导致可测量的宫颈癌几乎完全消失。
ODE-PMEG 可能适合局部或局部治疗宫颈发育不良。
