Pan Xing Q, Shih Chu C, Harday John
College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Anticancer Res. 2005 Sep-Oct;25(5):3167-72.
It has long been known that the polycarbohydrates on the neoplastic cell surface are different from those on normal cells; differences which allow one to attack tumor cells selectively. Although the exact differences between tumor cells and normal cells are still not clearly known, research into these differences is ongoing for anticancer drug development.
The human breast cancer cell line MCF-7 in culture and human breast xenograft B(11)-2 in SCID mice were used in our observations. Two different samples of chitinase from different bacteria were tested in the experiments. Optical observation of regular H & E-stained tumor tissue sections and observations by transmission electron microscopic techniques were used in this study.
MCF-7 breast cancer cells in culture showed structural damage within 7 hours after 1.3 unit/ml of chitinase was added to the medium, while normal mice spleen cells did not. The transplanted B(11)-2 xenograft tissue in mice started to lyse 12 hours after chitinase was injected; the size of the tumor gradually reduced and finally a scab was formed, which came off the skin a few days later. All the tested tumor-bearing mice survived and these cured mice had no tumor re-growth during the following 1-year observation period.
Chitinase selectively lysed the tumor cells in vitro and in vivo. Injected chitinase destroyed the tumor tissue and cured the mice. The further development of this type of treatment and of the mechanisms of chitinase action are discussed.
长期以来人们都知道,肿瘤细胞表面的多碳水化合物与正常细胞表面的不同;这些差异使得人们能够选择性地攻击肿瘤细胞。尽管肿瘤细胞与正常细胞之间的确切差异仍不清楚,但针对这些差异的研究正在进行,以开发抗癌药物。
我们的观察使用了培养的人乳腺癌细胞系MCF-7和SCID小鼠体内的人乳腺异种移植瘤B(11)-2。实验中测试了来自不同细菌的两种不同的几丁质酶样本。本研究采用常规苏木精和伊红染色肿瘤组织切片的光学观察以及透射电子显微镜技术观察。
向培养基中加入1.3单位/毫升的几丁质酶后,培养的MCF-7乳腺癌细胞在7小时内出现结构损伤,而正常小鼠脾细胞未出现。给小鼠注射几丁质酶后12小时,移植的B(11)-2异种移植瘤组织开始溶解;肿瘤大小逐渐缩小,最终形成痂皮,几天后从皮肤上脱落。所有受试荷瘤小鼠均存活,且这些治愈的小鼠在随后1年的观察期内肿瘤未复发。
几丁质酶在体外和体内均能选择性地溶解肿瘤细胞。注射几丁质酶可破坏肿瘤组织并治愈小鼠。本文讨论了这类治疗方法的进一步发展以及几丁质酶作用的机制。