Andrei G, Snoeck R, Piette J, Delvenne P, De Clercq E
Rega Institute for Medical Research, Katholieke Universiteit, Leuven, Belgium.
Oncol Res. 1998;10(10):533-9.
At present more than 70 human papillomaviruses (HPV) genotypes have been described and each shows a predilection for a cutaneous or mucosal surface. There is a strong association between infection with specific genital viruses (i.e., types 16 and 18) and the development of cervical cancer. Thus, intervention with the natural history of HPV infection in the genital tract may form the basis for an effective anticancer strategy. We have shown that treatment of cell lines derived from human cervical carcinomas [i.e., SiHa and CaSki (HPV-16-positive)] and HeLa (HPV-18-positive)] with HPMPC (cidofovir) results in a concentration- and time-dependent inhibition of cell proliferation. We report here the effects of HPMPC on the growth of cervical carcinoma (SiHa) xenografts in athymic nude mice. Athymic mice between the age of 6 and 8 weeks were injected SC with 5 to 10x10(6) cells. Once tumors were established, the mice were injected with PBS (placebo), HPMPC, or cytarabine (AraC) at the tumor site. Animals that were injected intratumorally with HPMPC at a dose of 5 mg/ml (0.25 mg/injection) or 10 mg/ml (0.5 mg/injection) three or five times per week, once daily, during 4 weeks showed a statistically significant reduction in tumor size compared to the placebo group or AraC group. However, when HMPC was administered topically (as a cream) or systemically (intraperitoneally), no reduction of tumor growth was observed at nontoxic concentrations, suggesting that a high local concentration of HPMPC is required to achieve a significant decrease of tumor growth.
目前已发现70多种人乳头瘤病毒（HPV）基因型，每种基因型都倾向于感染皮肤或黏膜表面。特定的生殖器病毒（即16型和18型）感染与宫颈癌的发生密切相关。因此，干预生殖道HPV感染的自然病程可能成为一种有效的抗癌策略的基础。我们已经表明，用HPMPC（西多福韦）处理源自人宫颈癌的细胞系[即SiHa和CaSki（HPV - 16阳性）]以及HeLa（HPV - 18阳性）]会导致细胞增殖受到浓度和时间依赖性的抑制。我们在此报告HPMPC对无胸腺裸鼠中宫颈癌（SiHa）异种移植瘤生长的影响。给6至8周龄的无胸腺小鼠皮下注射5至10×10⁶个细胞。一旦肿瘤形成，在肿瘤部位给小鼠注射PBS（安慰剂）、HPMPC或阿糖胞苷（AraC）。每周三次或五次、每次剂量为5mg/ml（0.25mg/注射）或10mg/ml（0.5mg/注射）、持续4周瘤内注射HPMPC的动物，与安慰剂组或AraC组相比，肿瘤大小有统计学意义的减小。然而，当局部（作为乳膏）或全身（腹腔内）给予HMPC时，在无毒浓度下未观察到肿瘤生长的减缓，这表明需要高局部浓度的HPMPC才能显著降低肿瘤生长。
