Donmez C, Groves M J
Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago (M/C 964) 60607-7019, USA.
Anticancer Res. 1997 Jan-Feb;17(1A):445-50.
Attenuated Mycobacterium bovis, Bacillus Calmette Guerin, BCG vaccine, is a general immune stimulant and is now an approved clinical treatment for superficial bladder cancer. Isolation and characterization of a series of complex polysaccharides (glycans) from BCG and other mycobacteria has shown that these materials are remarkably heat stable and have considerable in vivo activity against a number of animal cancer models. This present communication describes the testing of a glycan, PS1, obtained from the Tice substrain of BCG against the hormonal dependent human breast cancer cell line MCF-7 and the hormonally independent BT-20 line, using 5-fluorouracil (5-FU) as a positive control.
The PS1 was obtained by methods previously described. Cells were obtained from the American Type Culture Collection (Rockville, MD) and athymic nu/nu mice from Frederick (MD). The cells were implanted into the flanks of 20g female nude mice (n = 10). After two weeks, volumes of phosphate buffered saline (control), 5-FU (positive control) or PS1 solutions were injected and the tumor growth rates followed for up to six weeks.
The 5-FU was effective in slowing tumor growth of both tumors. The MCF-7 cell line was markedly affected by the PS1, especially in the presence of estradiol. The BT-20 cell line was only marginally affected by PS1, with or without estradiol.
Since PS1 is known to have macrophage stimulating activity and nude mice are deficient in both T-cells and natural killer cells, the mechanism of activity is postulated to involve MHC-1 antigen secretion by the hormonal-dependent tumor cells, enhanced in the presence of hormone. These cells are then actively identified and destroyed by local macrophages.
减毒牛分枝杆菌,即卡介苗(BCG)疫苗,是一种通用的免疫刺激剂,目前是浅表性膀胱癌的一种获批临床治疗方法。从卡介苗和其他分枝杆菌中分离和鉴定出一系列复杂多糖(聚糖),结果表明这些物质具有显著的热稳定性,并且在多种动物癌症模型中具有相当的体内活性。本通讯描述了用5-氟尿嘧啶(5-FU)作为阳性对照,对从卡介苗Tice亚株获得的聚糖PS1针对激素依赖性人乳腺癌细胞系MCF-7和激素非依赖性BT-20细胞系进行的测试。
PS1通过先前描述的方法获得。细胞购自美国典型培养物保藏中心(马里兰州罗克维尔),无胸腺裸鼠购自弗雷德里克(马里兰州)。将细胞植入20克雌性裸鼠(n = 10)的侧腹。两周后,注射磷酸盐缓冲盐水(对照)、5-FU(阳性对照)或PS1溶液,并跟踪肿瘤生长速率长达六周。
5-FU可有效减缓两种肿瘤的生长。MCF-7细胞系受到PS1的显著影响,尤其是在存在雌二醇的情况下。BT-20细胞系无论有无雌二醇,仅受到PS1的轻微影响。
由于已知PS1具有巨噬细胞刺激活性,且裸鼠缺乏T细胞和自然杀伤细胞,因此推测其活性机制涉及激素依赖性肿瘤细胞分泌MHC-1抗原,在激素存在时增强。然后这些细胞被局部巨噬细胞主动识别并破坏。