喷昔洛韦对宫颈癌细胞系抑制作用的研究  

Penciclovir Induced Inhibitory Effect on the Growth of Cervical Cancer Cells Carrying Human Papillomavirus

作　　者：陈连凤[1] 王淼[1] 王立良[1] 司静懿[1] 刘跃华[2] 王家璧[2] 

机构地区：[1]中国医学科学院中国协和医科大学基础医学研究所生物物理室,北京100005 [2]北京协和医院皮肤科

出　　处：《中国临床药理学杂志》2001年第2期110-113,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的：喷昔洛韦９位取代鸟嘌呤化合物，在体内外对单纯疱疾病毒Ⅰ型（ＨＳＶ－Ⅰ）、Ⅱ型（ＨＳＶ－Ⅱ），带状疱疹病毒（ＶＩＶ）有良好的抑制作用。我们从基础研究入手，在细胞水平上探讨喷昔洛韦对ＨＰＶ（人乳头瘤病毒）相关细胞系的作用，为扩大此药的治疗适应症提供新的思路。方法：采用不同来源的宫颈癌细胞系ＣａＳｋｉ（ＨＰＶ１６型阳性的人宫颈鳞状上皮细胞系）、Ｈｅｌａ（ＨＰＶ１８型阳性的人宫颈腺上皮细胞系）、 Ｎ（由 ＨＰＶ１６ Ｅ６／ｅ７基因和 ＨＳＶ的 Ｎ片断共转染得到的恶性转化宫颈鳞状上皮细胞系）和２ＢＳ（人正常纤维细胞）及原代培养的正常人鳞状上皮细胞，加入不同浓度的喷昔洛韦，测定不同细胞在喷昔洛韦药物作用下的半数致死浓度（ＥＤ５０），喷昔洛韦对上述细胞的ＥＤ５０分别是２．５ × １０－３ｍｏＬ·Ｌ－１， ７·５ × １０－３ｍｇ·Ｌ－１， ２５ × １０－３ｍｇ·Ｌ－１５．０ × １０－３ｍｇ·Ｌ－１， １５．０ × １０－３ｍｇ·Ｌ－１。选择合适的喷昔洛韦浓度加到各种细胞系中，在不同时间下，用倒置显微镜观察细胞的形态结构改变及测定了各种细胞的生长速度（生长曲线），用透射电子显微镜观察了细胞的超微结构变化。结果：选择 ７．５ ×１０－?OBJECTIVE : Penciclovir, a guanosine analogue with 9 site substitution, is a newly developed anti-virus compound, which shows significant inhibitory effects on HSV-Ⅰ/Ⅱ and VIV in vivo and in vitro. TO expand the therapeutic adaptive diseases we investigated roles of PCV on several cell lines carrying HPV(human papillomavirus). METHODS:Using cervix-derived cell lines of CaSki (HPV16 positive squamous epithelial cells), Hela(HPV18 positive glandular epithelial cells), N(squamous epithelial cells transformed by HPV16 E6/E7 genes and HSV N fragment), fibril cell line 2BS and primary culture of normal epithelial cell we determined PCV ED,, and observed the cell structure changes with light and electronic microscope at different times after addition of PCV RESULTS:ED50 of thecells above was 2.5 × 10-3 moL.L-1, 7.5 × 10-3 moL.L-1, 2.5 × 10-3 moL·L-1, 5.0 × 10-3 moL·L-1 and 15.0 × 10-3 moL·L-1,respectively At the concentration of 7.5 × 10-3mol·L-1,N cells(positive control) and CaSki began to die at 24h after administration of 7.5 × 10-2moL·L-1, PCV and almost all lysed at the 4th day of administration, showing PCV has strong inhibitory effects on squmous epithelial cells. PCV showed less inhibitory effects on HeLa, no effects on primary culture of normal epithelial cells in contrary to the strong inhibitory effects on 2BS. The ultra-structure of the HPV-related cells above showed typical inhibited morphological changes. CONCLUSIONS:PCV has inhibitory effects on HPV related cells, indicating its potential use in therapy of HPV caused diseases.

关 键 词：喷昔洛韦 宫颈癌细胞系 药物治疗 抑制作用 HPV 

分 类 号：R737.33[医药卫生—肿瘤] R978.7[医药卫生—临床医学]